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  • Digitale Medien  (5.034)
  • Loseblatt
  • 1990-1994  (5.034)
  • Biochemistry and Biotechnology  (4.119)
  • Rat  (915)
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  • Digitale Medien  (5.034)
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  • 101
    Digitale Medien
    Digitale Medien
    A comparison of the effects of the D1 receptor antagonists SCH 23390 and SCH 39166 on suppression of feeding behavior by the D1 agonist SKF38393 (1994)
    Springer
    Psychopharmacology 113 (1994), S. 328-333 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Dopamine ; 5-HT2 ; 5-HT1C ; D1 ; SKF 38393 ; SKF 82958 ; SCH 39166 ; SCH 23390 ; Feeding ; Behavior ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The hypophagic effect of the D1 receptor agonist SKF 38393 is not dose-dependently antagonized by the D1 antagonist SCH 23390. Moreover, the receptor specificity of this interaction remains in question, since SCH 23390 has significant activity at both 5-HT2 and 5-HT1C receptors, and SKF 38393 also interacts with 5-HT1C receptors. To determine the relative significance of these actions, a comparison was made between the anorectic effects in rats of SCH 23390 (0.1–1.0 mg/kg) and the benzonaphthazepine SCH 39166 (0.1–3.0 mg/kg), a D1 antagonist with negligible affinity for 5-HT sites. Both compounds inhibited food-intake dose-dependently, with SCH 23390 being approximately twice as potent as SCH 39166. Behaviorally inactive and active doses of both antagonists were tested in combination with the D1 agonist SKF 38393 (10–56 mg/kg). Neither antagonist was able to produce more than a marginal attenuation of the agonist-induced hypophagia. This demonstrates that previous failures to reverse the behavioral actions of SKF 38393 by SCH 23390 were not due to specific actions of this particular antagonist. Finally, like SCH 23390, SCH 39166 (0.3 mg/kg) was able to attenuate fully the anorectic effects of the D1 agonist SKF 82958 (1.0 and 3.0 mg/kg), demonstrating that neither compound is intrinsically unable to block D1 receptor-mediated hypophagia. The results demonstrate the generality of the D1 antagonist-mediated effect on feeding and call into question the use of SKF 38393 as a D1 agonist in studies of feeding, and perhaps in other contexts as well.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245205
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  • 102
    Digitale Medien
    Digitale Medien
    Prenatal nicotine exposure increased duration of nicotine-induced analgesia in adult rats (1994)
    Springer
    Psychopharmacology 113 (1994), S. 534-538 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Nicotine ; Prenatal ; Analgesia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245235
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  • 103
    Digitale Medien
    Digitale Medien
    Methamphetamine exposure during early postnatal development in rats: I. Acoustic startle augmentation and spatial learning deficits (1994)
    Springer
    Psychopharmacology 114 (1994), S. 392-401 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Methamphetamine ; Rat ; Postnatal ; Acoustic startle ; Spatial learning
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Methamphetamine (MA) induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received less attention. In this experiment the effects of MA exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-MA (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited augmented acoustic startle and impaired performance in a complex multiple-T water maze. Only the early MA exposure group showed a persistent deficit in weight while only the later MA exposure group showed impaired learning in the Morris hidden platform maze. Effects on locomoter activity are reported in the accompanying article. It was concluded that the effects of MA are both long lasting and stage dependent and involve cognitive as well as arousal functions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02249328
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  • 104
    Digitale Medien
    Digitale Medien
    Influence of 5-HT3 receptor antagonists and the indirect 5-HT agonist, dexfenfluramine, on heroin self-administration in rats (1994)
    Springer
    Psychopharmacology 114 (1994), S. 611-619 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Heroin self-administration ; Rat ; 5-HT ; 2-HT3 receptor antagonists ; Ondansetron ; MDL72222 ; Indirect 5-HT agonist ; Dexfenfluramine ; Opioid reinforcement
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The purpose of the present study was to examine the effects of the 5-HT3 antagonists ondansetron and MDL72222, and the 5-HT releaser and reuptake inhibitor dexfenfluramine, on intravenous heroin self-administration by Wistar rats. Using separate squads of animals, two separate schedules of heroin reinforcement were used; a relatively low dose (0.03 mg/kg per infusion) made available under a FR5 schedule for 1 h each day, and a moderate heroin dose (0.1 mg/kg per infusion) available under a FR1 schedule for 2 h each day. Following the acquisition of stable levels of responding across days, both naloxone pretreatment (0.25 mg/kg SC) and halving the heroin infusion dose produced increases in operant responding for heroin at each concentration. Neither ondansetron (0.01–1 mg/kg SC) nor MDL72222 (0.1–3 mg/kg SC) pretreatment influenced heroin self-administration. Chronic treatment (5 day) of ondansetron (0.01–0.1 mg/kg) was similarly ineffective. However, dexfenfluramine (0.5–2.5 mg/kg IP) consistently reduced heroin self-administration at doses producing only modest decreases in food responding. These findings are in contrast to place conditioning studies, which show that 5-HT3 antagonists but not indirect 5-HT agonists block a morphine-induced place preference. Reasons for such discrepancies remain to be determined.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244992
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  • 105
    Digitale Medien
    Digitale Medien
    Effects of (R)-α-methylhistamine and scopolamine on spatial learning in the rat assessed using a water maze (1994)
    Springer
    Psychopharmacology 114 (1994), S. 651-656 
    Details
    ISSN: 1432-2072
    Schlagwort(e): (R)-α-Methylhistamine ; Scopolamine ; Histamine ; Cognition ; Water maze ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of (R)-α-methylhistamine ((R)-α-MeHA, a selective H3-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)-α-MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)-α-MeHA and SCOP, (R)-α-MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)-α-MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244997
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  • 106
    Digitale Medien
    Digitale Medien
    Ethological study of the effects of tetrahydroaminoacridine (THA) on social recognition in rats (1994)
    Springer
    Psychopharmacology 114 (1994), S. 644-650 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Social recognition ; Cognition ; Social interaction ; Ethological method ; Tetrahydroaminoacridine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Two major difficulties confront ethopharmacological investigations on cognitive abilities such as social recognition in drug-treated animals involved in free social interactions. The first concerns the choice of the most relevant behaviours, those reflecting the cognitive abilities attributed to the animals and assessing the specificity of the drug activity, and those reflecting non-specific drug effects. The second refers to the experimenter's awareness that in contrast to physical objects, social stimuli respond to drug-treated subjects and that their own level of responsiveness may influence the changes of drug-treated subjects' social interest. In addition, their contribution may vary according to the different treatments the drug-treated subjects receive. In examining the effects of tetrahydroaminoacridine (THA) at doses of 0.3, 1 and 3 mg/kg on the ability of adult male rats to recognize previously encountered conspecifics, we attempted to take into consideration such difficulties. A detailed behavioural profile of drug-treated rats was reported to separate specific from non-specific effects of THA. In addition, rats were assigned an index of responsibility for contact which takes into account the interactive dimension of each dyad and allows relevant comparisons between different treatments. The doses of THA which were found to decrease the duration of exploration of a familiar juvenile were also found to decrease the number of contacts initiated by the drug-treated subjects. THA induced a relative increase in body care by comparison to saline treatment. However, it had no effect of locomotor activity and rearing of the subjects. These findings enable dissociation of the effects of THA on cognitive versus non-cognitive processes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244996
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  • 107
    Digitale Medien
    Digitale Medien
    Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats (1994)
    Springer
    Psychopharmacology 115 (1994), S. 249-253 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Penile erection ; Muscimol ; Baclofen ; Bicuculline ; Picrotoxin ; Phaclofen ; Apomorphine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01–0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1–0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244779
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  • 108
    Digitale Medien
    Digitale Medien
    Microcatalepsy and disruption of forelimb usage during operant behavior: differences between dopamine D1 (SCH-23390) and D2 (raclopride) antagonists (1994)
    Springer
    Psychopharmacology 115 (1994), S. 24-30 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Dopamine receptors ; Neuroleptics ; SCH-23390 ; Raclopride ; Response duration ; Catalepsy ; Operant behavior ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In an experiment designed to distinguish between the behavioral consequences of treatment with SCH-23390, a D1 dopamine receptor blocker, and raclopride, a D2 antagonist, rats were trained to perform a water-reinforced forelimb operant response. Response rate and the duration of each forelimb contact with the operandum were recorded. In addition, the durations of the rat's visits to the reward well were detected by a photobeam which was blocked by the rat's muzzle as it remained at the reward well. In a between-groups dosing design, separate groups of rats (11–13 rats/group) received SCH-23390 (0, 0.01, 0.02, 0.04, 0.08, 0.12 mg/kg, IP, 30 min) or raclopride (0. 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg, IP, 30 min) for 21 consecutive days. Quantitative analyses indicated that for comparable amounts of operant rate reduction, raclopride had a significantly greater tendency than SCH-23390 to increase the duration of operant responses and to increase the maximum muzzle entry duration (i.e., to induce microcatalepsy). The results support the idea that at relatively low doses D2 antagonism is more likely than D1 antagonism to produce effects identified preclinically with extrapyramidal side effects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244747
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  • 109
    Digitale Medien
    Digitale Medien
    Behavioural and pharmacological characterisation of the elevated “zero-maze” as an animal model of anxiety (1994)
    Springer
    Psychopharmacology 116 (1994), S. 56-64 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Anxiety ; Elevated zero-maze ; Rat ; Diazepam ; Chlordiazepoxide ; mCPP ; 8-OH-DPAT ; Ondansetron ; Head dips ; Stretched attend postures
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The elevated “zero-maze” is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125–0.5 mg/kg) and chlordiazepoxide (0.5–2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drugm-chlorophenyl-piperazine (mCPP; 0.25–1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001–0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001–1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel “zero-maze” design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244871
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  • 110
    Digitale Medien
    Digitale Medien
    Effects of SR 48692, a selective non-peptide neurotensin receptor antagonist, on two dopamine-dependent behavioural responses in mice and rats (1994)
    Springer
    Psychopharmacology 116 (1994), S. 237-241 
    Details
    ISSN: 1432-2072
    Schlagwort(e): SR 48692 ; Neurotensin receptor antagonist ; Dopamine ; Apomorphine ; Bromocriptine ; (+) SKF 38393 ; (+) Amphetamine ; Turning ; Yawning ; Mouse ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04 – 0.64 mg/kg orally), antagonizes (50–65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 µg), (+) SKF 38393 (0.1 µg), bromocriptine (0.01 ng) or (+) amphetamine (10 µg) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245067
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  • 111
    Digitale Medien
    Digitale Medien
    Atropine effects on the intermediate stage and paradoxical sleep in rats (1994)
    Springer
    Psychopharmacology 116 (1994), S. 304-308 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Intermediate stage of sleep ; Paradoxical sleep ; Spindle ; Theta rhythm ; Atropine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Paradoxical sleep (PS) in the rat, cat and mouse is preceded and sometimes followed by a short-lasting intermediate stage (IS) characterized by high amplitude cortical spindles and low frequency theta rhythm. This stage, which is mimicked by an intercollicular transection, is massively extended at the expense of PS by low doses of barbiturates. Since the pontine cholinergic cell activation of PS is suppressed by barbiturates, we studied whether atropine, an antimuscarinic compound, extends IS at the expense of PS. Atropine sulfate was given at 5, 10 and 20 mg/kg IP. All doses increased dose dependently the occurrence latency of IS and PS. The amount of IS and PS was decreased for several hours, principally by a decrease of the number of phases. At 20 mg/kg the phase mean duration of IS and PS was also decreased. Consequently, IS and PS are similarly supported by muscarinic processes. The theta rhythm frequency was scored during IS and outside PS phasic motor activities (type 2 theta). At all doses it was significantly increased for hours. The theta rhythm frequency was also transiently increased during the hypersynchronization periods of PS (type 1 theta). At 20 mg/kg it was similarly the case for type 1 theta rhythm during waking.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245333
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  • 112
    Digitale Medien
    Digitale Medien
    Investigations of fetal development models for prenatal drug exposure and schizophrenia. Prenatald-amphetamine effects upon early and late juvenile behavior in the rat (1994)
    Springer
    Psychopharmacology 116 (1994), S. 226-236 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Fetus ; Prenatal drug exposure ; Schizophreniad-Amphetamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Recent evidence suggests that mid-pregnancy is a critical period for production of fetal abnormalities that cause behavioral and neuropathological changes in adult offspring. The present experiments provide an animal model of these effects by treating pregnant Sprague-Dawley rats during gestational days 11–14 withd-amphetamine (AM). Offspring were tested for neurological signs, foraging activity, reversal learning, and sensitivity to amphetamine challenge. In the Early Juvenile period, postnatal days (PND) 20–30, female AM offspring initially showed reductions in rearing, holepoking, and midfield activity. On later trials, and as young adults, AM females showed signs of locomotor hyperactivity despite continued poor foraging efficiency, and were also more sensitive to a 1.0 mg/kgd-amphetamine challenge. AM males showed initially slower and more perseverative responding than controls, but then developed excessive response switching. These changes continued during tests for Retention, Reversal, and Extinction in the Late Juvenile/Early Adult stage (PND 50–90), when both AM-exposed sexes showed increased eating time, significantly more perseverative lateral turning preference (right or left), and slower reversal learning than controls. Behavioral data were consistent with aberrations in thalamo-frontal and mesolimbic/nigrostriatal projection systems that have been reported in AM animals and which are also affected by maternal drug abuse and schizophrenia.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245066
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  • 113
    Digitale Medien
    Digitale Medien
    Chronic haloperidol treatment leads to an increase in the intramembrane interaction between adenosine A2 and dopamine D2 receptors in the neostriatum (1994)
    Springer
    Psychopharmacology 116 (1994), S. 279-284 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Adenosine A2 receptor ; Dopamine D2 receptor ; Methylxanthine ; Tardive dyskinesias ; Receptor-receptor interaction ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G protein. This intramembrane A2-D2 interaction might be responsible for the behavioural depressant effects of adenosine agonists and for the behavioural stimulant effects of adenosine antagonists such as caffeine and theophylline. Dopamine denervation induces an increase in the intramembrane A2-D2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in these animals. The present study was designed to examine if chronic treatment with haloperidol, which also produces dopamine receptor supersensitivity, is also associated with an increase in the intramembrane A2-D2 interaction in the neostriatum and with a higher sensitivity to the behavioural effects induced by adenosine antagonists. The data showed that: (i) haloperidol pretreatment causes a higher binding of the D2 antagonist [3H] raclopride in striatal membrane preparations due to an increase in the number of D2 receptors without changes in their affinity for the antagonist (increase in Bmax without changes in kd); (ii) GCS 21680 decreases the affinity of dopamine for the D2 receptor, by increasing the equilibrium dissociation constants of high (Kh) and low affinity (K1) dopamine D2 binding sites and increases the proportion of high affinity binding sites (Rh); (iii) a low dose of CGS 21680 (3 nM), which is ineffective in membrane preparations from neostriatum of nontreated animals, is effective in membranes from the striatum of haloperidol-pretreated animals; (iv) the nonselective adenosine antagonist theophylline (20 mg/kg SC) causes a higher motor activation in rats pretreated with haloperidol. The possible relevance of these results for the pathophysiology and treatment of tardive dyskinesias is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245329
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  • 114
    Digitale Medien
    Digitale Medien
    Adrenalectomy increases local cerebral blood flow in the rat hippocampus (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 183-188 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Hippocampus ; Corticosterone ; Adrenalectomy ; Local cerebral blood flow ; Diurnal rhythm ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present study examined the effect of glucocorticoid manipulations on local cerebral blood flow in the hippocampus. We measured local cerebral blood flow in the hippocampus at 1-h intervals over a 1-day period in freely moving rats, by means of the H2 clearance method, before and after sham adrenalectomy, adrenalectomy or adrenalectomy with corticosterone replacement. We also measured local cerebral blood flow in the prefrontal cortex before and after adrenalectomy. Four weeks after the adrenalectomy, hippocampal blood flow at each time of day was an average of 47% greater than before the operation, showing diurnal variation as before. After the sham adrenalectomy or adrenalectomy with corticosterone replacement, hippocampal blood flow did not change significantly with respect to either its level or its diurnal variation. Local cerebral blood flow in the prefrontal cortex increased by only 19% after adrenalectomy. The present study demonstrates that adrenalectomy causes a remarkable increase in hippocampal blood flow, probably due to a lack of corticosterone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00374770
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  • 115
    Digitale Medien
    Digitale Medien
    Exercise-induced necrotic muscle damage and enzyme release in the four days following prolonged submaximal running in rats (1994)
    Springer
    Pflügers Archiv 428 (1994), S. 346-351 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Skeletal muscle ; Muscle damage ; Treadmill running ; Serum ; Enzymes ; Water content ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Male Wistar rats were made to run uphill on a treadmill 5.5° incline at 17 m min−1 for 4 h, and killed for muscle and serum sampling 2, 4, 12, 24, 48 or 96 h after the exertion. To estimate the degree of muscle damage,β-glucuronidase activity, total protein concentration, water content and morphology were examined in the red parts of quadriceps femoris (MQF) and soleus (MS) muscles, the distal white part of the rectus femoris muscle (MRF) and the superficial part of triceps brachii muscle (MTB). Simultaneous serum samples were assayed for creatine kinase (CK) activity and carbonic anhydrase III (CA III) concentration. Fibre swelling and interstitial oedema were detected in MS at 4 h and in MQF at 12 h and typical histopathological changes, including inflammation and fibre necrosis, in both muscles 12–96 h post-exertion.β-Glucuronidase activity, a quantitative marker of muscle damage, was increased in MS at 4 h, in MQF at 24 h and in MRF 48 h after the running. No increase occurred in MTB. Water and protein content increased or decreased respectively, faster in MS (2 h post-exercise) than in MQF (12 h) or MRF (12 h). Water content thus contributed to muscle damage by preceding the increase inβ-glucuronidase activity. Serum CK activity was increased 2, 4, and 48 h after the running. Changes in serum CA III concentration were rather similar to those in CK but were not significant. The increase in serum CK was not in concert with the necrotic events in the muscle but occurred considerably earlier (2 h vs. 12–24 h post-exercise). The second peak in CK, 48 h post-exercise (during the necrotic phase), was smaller than the first one. Our results show that serum CK activity is an inaccurate estimate of exercise-induced muscle damage as regards interpretation of the degree and the time course of pathological events in the muscle.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00724517
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  • 116
    Digitale Medien
    Digitale Medien
    An interaction between glucose and estrogen in gastric acid secretion in the lateral hypothalamic area of female rats (1994)
    Springer
    Experimental brain research 102 (1994), S. 171-174 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Estrogen ; Gastric acid secretion ; Glucose ; Hypothalamus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Gastric acid outputs caused by glucose injection into the lateral hypothalamic area (LHA) were examined in insulin hypoglycemia with or without estradiol-17β (EST) administration in bilaterally ovariectomized (OV) female rats. The basal level of acid output was higher in OV rats without EST than in OV rats with EST. When acid response was expressed as the percentage change, glucose injection into the LHA decreased acid output in a dose-dependent fashion in OV rats, while, in OV rats with EST, glucose injection into the LHA also reduced acid output without dose dependency. It was also noted that the threshold concentration of glucose that induced an acid response was lower in OV rats without EST than in OV rats with EST. These findings suggest that glucose-sensitive neurons responsible for gastric acid secretion can be modulated by estrogen at the LHA level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00232450
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  • 117
    Digitale Medien
    Digitale Medien
    Subthreshold rectification in neostriatal spiny projection neurons (1994)
    Springer
    Experimental brain research 100 (1994), S. 239-249 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Neostriatum ; In vitro brain slices Inward rectification ; Subthreshold ion conductances Firing pattern ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Intracellular recordings from slice preparations were used to assess the subthreshold electrophysiological behavior of rat neostriatal projection neurons. Both current steps and ramp currents were used to estimate the current-voltage relationship (I–V plot). Inward rectification in the subthreshold range was a characteristic of most neurons. The amount of rectification varied greatly, and it was complex: membrane voltage trajectories in response to ramps were made up by almost piecewise changes in the rate of voltage rise, suggesting that multiple conductances contribute to the subthreshold range. Inward current blockers such as tetrodotoxin (TTX) or Cd2+ decreased inward rectification, whereas outward current blockers such as tetraethylammonium (TEA) or 4-aminopyridine (4-AP) increased inward rectification. However, most inward rectification was due to TEA- and Cs+-sensitive conductances and not to TTX- or Cd2+-sensitive conductances. Cs+-sensitive conductances predominated at more negative membrane potentials, whereas 4-AP-sensitive conductances predominated at just ±10 mV below the firing threshold. In spite of a very slow activation, there was evidence for transient outward currents modulating the response, i.e., 4-AP-sensitivity, and voltage-sensitivity for firing frequency and threshold. TEA-sensitive conductances also contributed toward fixing the firing threshold. These results imply the contribution of various ion conductances on the shaping of the characteristic physiological firing recorded in vivo. Modulation of these responses by transmitters or peptides may help to understand neural processing in the neostriatum.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00227194
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  • 118
    Digitale Medien
    Digitale Medien
    Re-initiated growth from mature ventral mesencephalon: an in oculo transplant study of nigrostriatal co-grafts (1994)
    Springer
    Experimental brain research 101 (1994), S. 73-85 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Substantia nigra ; Striatum ; Transplant Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The ability of mature dopaminergic neurons derived from ventral mesencephalon to re-initiate growth after making contact with a non-innervated target was studied using the intra-ocular grafting model. Foetal ventral mesencephalic tissue or brain stem including the locus coeruleus area was grafted to the anterior chamber of the eye. Two weeks, 6 weeks or 1 year after the first implantation, foetal striatal tissue was placed in contact with the nigral graft or grafted alone. The size of the transplants was measured through the cornea. The final size of the striatal grafts was significantly larger when placed alone than when co-grafted with 1-year-old or 6-week-old dopaminergic grafts. Striatum grafted together with 2-week-old nigra was larger than when grafted adjacent to mature substantia nigra, but not significantly so. Nerve fibre outgrowth into the iris from the nigral transplants did not increase after maturation, but the re-innervated area of the host iris progressively increased around the locus coeruleus grafts. Ingrowth of tyrosine hydroxylase (TH) immunoreactive nerve fibres into the striatal grafts was studied 6 weeks after the second implantation. TH immunohistochemistry revealed innervation of the striatal piece in all cases, except for the group where striatum alone was grafted. With the short survival time for cografts of 6 weeks, TH-positive nerve fibres innervated a larger volume, had a patchy appearance and the density was higher in striatum grafted to 2 week-old nigral transplants than that seen in striatal transplants grafted to mature nigral grafts. The patchy pattern of TH-immunoreactive nerve terminals was also seen in striatum co-grafted with 6-week-old or 1-year-old nigral transplants. No difference in striatal innervation volume was detected between those latter two groups. When striatum was implanted adjacent to mature ventral mesencephalon and grown together for 6 months — the longer survival time — the same dense TH-positive innervation as seen in striatum co-grafted with immature nigral tissue at the shorter survival time was found. Additionally, the nigral part of the co-grafts showed increased TH-immunoreactive nerve fibre density. In conclusion, dopaminergic neurites from mature ventral mesencephalic transplants can re-initiate growth if placed in contact with non-innervated striatal tissue. The nigral grafts do not progressively re-innervate the host iris, while locus coeruleus grafts do. The intra-ocular grafting model can be used to study the in vivo effects of trophic factors on mature dopaminergc neurons.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00243218
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  • 119
    Digitale Medien
    Digitale Medien
    Threshold-spacing in motoneurone pools of rat and cat: possible relevance for manner of force gradation (1994)
    Springer
    Experimental brain research 102 (1994), S. 69-74 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Motoneurone ; Recruitment ; Force modulation ; Rat ; Cat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the context of an analysis concerning factors of importance for the relative contributions of recruitment and rate gradation of muscle force, the distribution of electrical excitability was analyzed for medial gastrocnemius (MG) motoneurones of rat and cat. The experimental data came from previously collected intracellular measurements in animals anaesthetized with pentobarbitone. Electrical excitability was measured as the threshold (nanoamperes) for single spike generation (rheobase) in rat and for maintained repetitive firing (rhythmic threshold) in cat. Furthermore, the data included measurements of axonal conduction velocity and of contractile properties of the muscle units innervated by the studied motoneurones. The units were categorized into types S (slow-twitch, fatigue-resistant), FR (fast-twitch, fatigue-resistant) and FF (fast-twitch, fatiguable) on the basis of the combined criteria of twitch-speed and sensitivity to fatigue. We confirmed that, in spite of the presence of normal-looking symmetrical distributions of axonal conduction velocity, there was a positive skew in the distribution of electrical excitability (relatively high numbers of cells with low thresholds, few with high ones). Within each unit category (S, FR, FF), we ranked the motoneurones according to their relative electrical excitability and calculated the threshold difference between consecutive cells (“threshold spacing”). In accordance with the skewed distribution of electrical excitability, we found that the mean threshold spacing was ranked in the same way as the mean thresholds, i.e. S〈FR〈FF; the statistical analysis showed that, for cats as well as rats, small threshold-spacing steps were significantly more common for S than for FF motoneurones. In the discussion it is pointed out that the narrow threshold-spacing for S units, as compared to FF units, would tend to decrease the relative amount of recruitment-parallel rate modulation in these cells. Thus, the spacing of recruitment thresholds tends to allow the easily recruited S motoneurones to remain firing at relatively low rates during ongoing recruitment gradation, which would be of potential value in promoting a high degree of endurance for long-lasting postural contractions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00232439
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  • 120
    Digitale Medien
    Digitale Medien
    Sensorimotor transformation in a spinal motor system (1994)
    Springer
    Experimental brain research 100 (1994), S. 170-174 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Withdrawal reflexes ; Motion analysis Nociception ; Pain ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To use sensory information from the skin to guide motor behaviour the central nervous system must transform sensory coordinates into movement coordinates. As yet, the basic principles of this crucial neural computation are unclear. One motor system suitable as a model for the study of such transformations is the spinal withdrawal reflex system. The spatial organization of the cutaneous input to these reflexes has been characterized, and we now introduce a novel method of motion analysis permitting a quantitative analysis of the spatial input-output relationship in this motor system. For each muscle studied, a “mirror-image” relationship was found between the spatial distribution of reflex gain for cutaneous input and the pattern of cutaneous unloading ensuing on contraction. Thus, there is an “imprint” of the movement pattern on this motor system permitting effective sensorimotor transformation. This imprint may indicate the presence of a learning process which utilizes the sensory feedback ensuing on muscle contraction.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00227291
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  • 121
    Digitale Medien
    Digitale Medien
    Expression of major histocompatibility complex class II antigen on amoeboid microglial cells in early postnatal rat brain following intraperitoneal injections of lipopolysaccharide (1994)
    Springer
    Experimental brain research 100 (1994), S. 287-292 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Amoeboid microglia Major histocompatibility complex Type 3 complement receptor ; Endotoxin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In rats given two single intraperitoneal injections of lipopolysaccharide (LPS) at 1 and 4 days of age and killed at 7 days of age, 11.5–12% of amoeboid microglial cells (AMC) in the supraventricular corpus callosum were induced to express major histocompatibility complex (MHC) class II antigen, as detected with monoclonal antibody OX-6. The MHC class II antigen induced was colocalized with MHC class I antigen and type 3 complement receptors on the same cells. The expression of MHC class II antigen on the plasma membrane of AMC was confirmed in immunoelectron microscopy. Although OX-6-positive AMC often assumed a perivascular position, the majority of them, however, were far removed from the blood vessels. The cytoplasmic processes of the perivascular OX-6-positive AMC appeared to rest directly on the vascular lamina, and in some section profiles they were in contact with a large surface area of the outer wall of small blood vessels. It is concluded from this study that although MHC class II antigen is not constitutively present on AMC, it is, however, inducible under stimulation with LPS. It is, therefore, suggested that the OX-6-positive AMC, especially the perivascular AMC, may have the potentiality to function as antigen-presenting cells in the developing brain when challenged by LPS.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00227198
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  • 122
    Digitale Medien
    Digitale Medien
    Lowering of extracellular pH suppresses low-Mg2+-induces seizures in combined entorhinal cortex-hippocampal slices (1994)
    Springer
    Experimental brain research 101 (1994), S. 44-52 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Acidosis ; Seizures ; Brain slices ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Lowering [Mg2+]o induces epileptiform bursting in hippocampus and entorhinal cortex (EC), presumably by activation of N-methyl-d-aspartate (NMDA) receptors. Since increasing [H+]o has been shown to reduce NMDA receptor activation, we hypothesized that this could contribute to anticonvulsant actions of acidic pH. To test this, we studied the effects of raising extracellular PCO2 (20.6%, pH = 6.7) or lowering extracellular pH (6.7 or 6.2) on low-Mg2+-induced epileptiform discharges. Lowering the pH to 6.7 by either means increased the interval between seizure-like events (SLEs), decreased the maximal amplitude of SLEs, and, if the site of seizure generation was at a distance from the recording site, acidification slowed the rate of seizure propagation. In contrast, the duration of SLEs was unaffected by acidic pH or high PCO2. Raising PCO2 or lowering pH to 6.7 also blocked early (8–10 min) but not late (〉 20 min) phases of status-like discharges. All effects of the extracellular pH changes were fully reversible. Further lowering of extracellular pH to 6.2 completely and reversibly blocked both SLEs and status-like discharges. Our data show that the effects of high PCO2 and low pH on seizures in the EC in vitro may be dose-dependent and consistent with induction by proton blockade of NMDA receptors. Thus, blockade of NMDA currents by protons may be an important component of the anticonvulsant action of extracellular acidosis. The results also suggest that acidosis may be a desirable property for new antiepileptic treatments.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00243215
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  • 123
    Digitale Medien
    Digitale Medien
    Phosphinic acid derivatives as baclofen agonists and antagonists in the mammalian spinal cord: an in vivo study (1994)
    Springer
    Experimental brain research 101 (1994), S. 59-72 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Spinal cord ; Synaptic transmission ; GABAB receptors ; Baclofen agonists and antagonists ; Rat ; Cat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre-and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35 348, 36 742, 46 381, 52 432, 54 626 and 55 845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABAA agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre-and postsynaptic inhibitory effects of 3-aminopropyl-methyl-osphinic acid (CGP 35 024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35 024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABAB receptors. Spinal pre-and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55 845 and 46 381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00243217
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  • 124
    Digitale Medien
    Digitale Medien
    Synaptic connectivity of serotonin graft efferents in the suprachiasmatic and supraoptic nuclei of the hypothalamus (1994)
    Springer
    Experimental brain research 101 (1994), S. 353-364 
    Details
    ISSN: 1432-1106
    Schlagwort(e): Transplantation ; Serotonin neurons ; Hypothalamus ; Electron microscopy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo-or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00227329
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  • 125
    Digitale Medien
    Digitale Medien
    Ibotenic acid lesions of the striatum reduce drug-induced rotation in the 6-hydroxydopamine-lesioned rat (1994)
    Springer
    Experimental brain research 101 (1994), S. 365-374 
    Details
    ISSN: 1432-1106
    Schlagwort(e): 6-Hydroxydopamine ; Ibotenic acid ; Rotation ; Amphetamine ; Apomorphine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Lesions of the dopaminergic nigrostriatal tract produce a range of motor and sensorimotor deficits. One of the simplest and most reliable is the rotational response of the animal following activation with drugs that stimulate the dopaminergic network, most notably amphetamine and apomorphine. Consequently, the rotation test has been extensively used in assessing the success of treatments designed to restore dopaminergic function, including neural transplants. The present study investigates whether rotation induced by 6-hydroxydopamine lesions of the nigrostriatal bundle in rats is modified by additional lesions in the neostriatum. It was found that apomorphine-induced rotation can be reduced by ibotenic acid lesions of the dopamine-deafferented striatum, and that the extent of the reduction was proportional to the size of the lesions. In contrast, such lesions produced a non-significant reduction in amphetamine-induced rotation, although the correlation between the extent of the reduction and the size of the lesion was again apparent. Since the pattern of change was similar in direction, albeit smaller in magnitude, than the previously reported effects of intrastriatal transplantation in rats with similar nigrostriatal lesions, rotation tests alone do not provide an unequivocal test of graft survival and function.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00227330
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  • 126
    Digitale Medien
    Digitale Medien
    Metabolism of a glucuronide conjugate of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats (1994)
    Springer
    Archives of toxicology 69 (1994), S. 14-17 
    Details
    ISSN: 1432-0738
    Schlagwort(e): Key words Tobacco-specific nitrosamine ; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone ; [4-(Methylnitrosamino)-1-(3-pyridyl)but-1-yl]- β-O-d-glucosiduronic acid ; Rat ; Urine ; Metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-β-O-d-glucosiduronic acid (NNAL-Glu) is another important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which has been detected in the urine of tobacco users and non-smokers heavily exposed to sidestream cigarette smoke. In order to evaluate the toxicological significance of NNAL-Glu formation and excretion, the metabolism of [5-3H]-NNAL-Glu was studied in rats. Five male F344 rats were administered 3.7 mg/kg [5-3H]-NNAL-Glu by i.v. injection and the metabolites in urine analysed by HPLC. More than 90% of the radioactivity was excreted in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2±3.1% of the total radioactivity; the remaining part of the dose appears to be deconjugated resulting in the urinary excretion of NNAL (3.6±1.7%) and its α-hydroxylation (11.5±2.2%) and N-oxidation (3.6±1.6%) products. The presence of α-hydroxylation products of NNAL-Glu in urine suggests that this NNK metabolite may be activated in vivo to carcinogenic intermediates.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002040050130
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  • 127
    Digitale Medien
    Digitale Medien
    Messenger RNA levels of lung extracellular matrix proteins during ozone exposure (1994)
    Springer
    Lung 172 (1994), S. 15-30 
    Details
    ISSN: 1432-1750
    Schlagwort(e): Rat ; DNA ; mRNA ; Collagen ; Fibronectin ; c-myc
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Continuous exposure of rats to ozone has been shown to result in lung epithelial damage, inflammation, and subsequent increases in collagen content. The main goal of this study was to identify the earliest time point of altered extracellular matrix protein gene expression by utilizing Northern blot analyses of rat lungs continuously exposed to 1.0 ppm ozone for 14 days. An early increase of steady-state fibronectin mRNA levels was observed at 2 days of exposure, prior to the time point of increased type I collagen mRNA, which was seen at 4 days. This increased level of type I collagen mRNA preceded measurable changes in total lung collagen content, observed at 7 days. In addition, peak levels of the growth-related proto-oncogene c-myc mRNA could be correlated with maximal increases of lung DNA content, although the initial increase in c-myc mRNA preceded measurable changes of total lung DNA. The use of specific cDNA probes for measuring altered gene expression can be useful for defining the early cellular and molecular events in ozone-induced lung injury.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00186166
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  • 128
    Digitale Medien
    Digitale Medien
    High-resolution magnetic resonance imaging of arthritic pathology in the rat knee (1994)
    Springer
    Skeletal radiology 23 (1994), S. 429-437 
    Details
    ISSN: 1432-2161
    Schlagwort(e): Arthritis ; Rat ; Knee ; MRI ; X-radiography ; histology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract High-resolution magnetic resonance imaging (MRI) has been used to visualise the changes that occur in both soft tissue and bone during antigen-induced, monoarticular arthritis (AIMA) of the rat knee. Extensive optimisation studies were performed in order to minimise the time of the experiments and to maximise both the signal-to-noise ratio and the contrast in the MR images. The study was cross-sectional rather than longitudinal and at each of the 13 time points studied during the progression of the disease, corresponding X-radiographs and histological sections were obtained. Interpretation of the spin echo MR images was aided by the use of chemical shift-selective imaging, magnetisation transfer contrast and relaxation time experiments, as well as by correlation with the histology and X-radiography data. The MR images clearly show invasion of the synovium by an inflammatory pannus which spreads over the articular cartilage and invades the bone, leading to erosion and later remodelling. Two distinct types of bony erosion were observed: focal erosions, especially at the margins of the joint, and subchondral erosions. It is concluded that MRI provides a sensitive, non-invasive method for investigating both early-stage inflammatory changes and late-stage bony changes in the knee joints of the arthritic rat.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00204603
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  • 129
    Digitale Medien
    Digitale Medien
    Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex (1994)
    Springer
    Psychopharmacology 113 (1994), S. 487-492 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Prefrontal cortex ; Dopamine ; Acoustic startle response ; Prepulse inhibition ; 6-Hydroxydopamine ; Rat ; Schizophrenia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 × 1 µl per side) of vehicle, a low (3.0 µg/µl) or a high (6.0 µg/µl) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245228
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  • 130
    Digitale Medien
    Digitale Medien
    Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with the fixed-interval peak procedure (1994)
    Springer
    Psychopharmacology 114 (1994), S. 463-468 
    Details
    ISSN: 1432-2072
    Schlagwort(e): 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Fixed-interval peak procedure ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Twelve rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats were then trained for 60 sessions under a discrete-trials fixed-interval schedule (peak procedure). In half the trials, a reinforcer became available 40 s after trial onset, and the trial was terminated upon reinforcer delivery; the remaining trials were 120 s in duration, and reinforcement did not occur in these trials. Performance during the 120-s trials was characterized by increasing response rate during the first 40 s of the trial, declining response rate between 40 s and 80 s, and a secondary increase in response rate during the final 40 s of the trial. The lesioned group showed a broader “spread” of the response rate function than the control group (time between attainment of 70% of the peak response rate and subsequent decline of response rate below this level); however, the peak response rate and the time from trial onset until attainment of the peak response rate did not differ significantly between the groups; the spread/peak-time ratio was significantly greater in the lesioned group than in the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02249337
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  • 131
    Digitale Medien
    Digitale Medien
    Crossmodal divided attention in rats: effects of chlordiazepoxide and scopolamine (1994)
    Springer
    Psychopharmacology 115 (1994), S. 213-220 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Divided attention ; Scopolamine ; Chlordiazepoxide ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract “Divided attention” is a psychological construct that hinges on assumptions about a fixed finite capacity of subjects to simultaneously process multiple sets of information. A model of a crossmodal divided attention task was developed in rats. Initially, rats were trained consecutively in operant auditory and visual conditional discrimination tasks. The final task consisted of two successive blocks of 20 trials per modality (modality certainty), followed by 60 trials comprising a semi-randomized sequence of stimuli of both modalities (auditory or visual) and qualities (flashing/pulsing or constantly turned on; modality uncertainty). In comparison to unimodal blocks of trials, performance in the mixed condition was assumed to reflect the demands on the parallel processing of two sets of stimulus-response rules. While response accuracy remained unchanged, response latencies were generally longer in the bimodal condition. Administration of scopolamine (0.03, 0.06, 0.1 mg/kg) or chlordiazepoxide (1, 3, 5, 8 mg/kg) dose-dependently increased response latencies. The scopolamine-induced increase in response latencies was greater in the mixed condition. Cost-benefit analyses demonstrated that the absolute divided attention costs (in ms) were generally higher for visual than for auditory stimuli. Both drugs produced qualitatively similar effects; however, scopolamine was more potent in increasing the absolute divided attention costs than chlordiazepoxide. These data are discussed in terms of the validity of this animal paradigm, and of hypotheses about the effects of benzodiazepine receptor agonists and muscarinic antagonists on brain information processing capacity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244774
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  • 132
    Digitale Medien
    Digitale Medien
    Diazepam impairs place learning in naive but not in maze-experienced rats in the Morris water maze (1994)
    Springer
    Psychopharmacology 115 (1994), S. 73-78 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Benzodiazepines ; Diazepam ; Morris water maze ; Place learning ; Anxiety ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02244754
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  • 133
    Digitale Medien
    Digitale Medien
    α2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats (1994)
    Springer
    Psychopharmacology 115 (1994), S. 478-484 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Aggression ; α2 Adrenoceptors ; Catecholamines ; ACTH ; Corticosterone ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245571
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  • 134
    Digitale Medien
    Digitale Medien
    Effects of cocaine microinjections into the nucleus accumbens and medial prefrontal cortex on schedule-induced behaviour: comparison with systemic cocaine administration (1994)
    Springer
    Psychopharmacology 115 (1994), S. 375-382 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Cocaine ; Schedule-induced polydipsia ; Drinking ; Locomotor activity ; Nucleus accumbens ; Medial prefrontal cortex ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of cocaine HCl infusions into either the nucleus accumbens (NACC) or medial prefrontal cortex (PFC) were compared on the performance of schedule-induced polydipsia (SIP) and related behaviours. Food-deprived rats were exposed to a fixed-time 60-s schedule of food delivery in daily 30-min sessions until stable levels of behaviour were obtained (14 days). Rats were then bilaterally infused with cocaine into either the NACC or PFC via chronically indwelling guide cannulae. Each subject received a sequence of five cocaine infusions (0, 12.5, 25, 50, 100 µg) according to a Latin Square design. For comparison, following these intracranial infusions each rat received a sequence of five IP injections of cocaine (0, 2.5, 5, 10, 20 mg/kg) also in a counterbalanced order. NACC and PFC infusions of cocaine and IP cocaine dose-dependently reduced SIP. Cocaine infusions into the NACC, but not the PFC, increased locomotor activity but the characteristic temporal profile of locomotor activity during SIP was retained. IP cocaine also increased locomotor activity in a dose-dependent manner, but the temporal profile of activity was flattened following 20 mg/kg cocaine. NACC and PFC infusions of cocaine had little effect on the total number of panel presses to gain access to the food pellets, but did slightly decrease the high rates of responding immediately prior to the pellet delivery. IP cocaine increased the total number of panel presses at the higher doses, mainly by increasing the low rates of responding. The effects of cocaine infusions into the PFC were behaviourally the most selective, as they reduced SIP without having substantial effects either on locomotor activity or panel pressing. These data therefore implicate a role for the PFC in the performance of SIP.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245080
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  • 135
    Digitale Medien
    Digitale Medien
    CCK-A and CCK-B selective receptor agonists and antagonists modulate olfactory recognition in male rats (1994)
    Springer
    Psychopharmacology 115 (1994), S. 435-440 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Behaviour ; Olfactory recognition ; Social investigation ; Neuropeptides ; Cholecystokinin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Modulation of learning and memory is one of the physiological roles that the neuropeptide cholecystokinin (CCK-8) may play. We have used a behavioural model of olfactory recognition among rats to test this hypothesis and to explore the relationship between CCK-A and CCK-B receptors and memory retention. Adult male rats form a transient memory of a juvenile congenere as indicated by a reduction in the duration of investigatory behaviour upon re-exposure 30 min after an initial exposure, but not when re-exposure is delayed until 120 min afterwards. In the present study, rats were treated after the first contact with various compounds; inhibition and facilitation of olfactory recognition were evaluated as the persistence in investigation 30 min and the decrease in investigation 120 min after pharmacological manipulations, respectively. Systemic injection of CCK-8, of a selective CCK-A agonist, or of non-peptide CCK-B antagonists (CI-988 and LY-262691) enhanced olfactory recognition. In contrast, the CCK-B selective agonist BC 264 and the tetrapeptide CCK-4 both disrupted it. Taken together with previous evidence of the detrimental effect of the non-peptide CCK-A antagonist devazepide on olfactory recognition, these results confirm and extend the hypothesis that there is a balance between CCK-A-mediated facilitative effects and CCK-B-mediated inhibitory effects on memory retention.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245565
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  • 136
    Digitale Medien
    Digitale Medien
    Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine (1994)
    Springer
    Psychopharmacology 115 (1994), S. 441-446 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Chronic mild stress ; Imipramine ; Animal model of depression ; Dopamine ; D1-receptors ; D2-receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245566
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  • 137
    Digitale Medien
    Digitale Medien
    Methamphetamine exposure during early postnatal development in rats: II. Hypoactivity and altered responses to pharmacological challenge (1994)
    Springer
    Psychopharmacology 114 (1994), S. 402-408 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Methamphetamine ; Rat ; Postnatal development ; Hypoactivity ; Pharmacological challenge
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Methamphetamine induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received little attention. In this experiment the effects of methamphetamine exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-methamphetamine (d-MA) (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited reduced locomotor activity. The effect was most evident at 30 days of age and was smaller at 45 and 60 days and only present at these latter ages in males. Only the early MA exposure group showed prolonged suppression of activity in response to a challenge dose of fluoxetine and a persistant deficit in weight while only the later MA exposure group showed attenuated suppression of activity in response to a challenge dose of fluoxetine. Based both on the present data and those in the preceding article, it was concluded that the effects of MA are both long lasting and stage dependent and involve arousal as well as cognitive functions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02249329
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  • 138
    Digitale Medien
    Digitale Medien
    5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task (1994)
    Springer
    Psychopharmacology 116 (1994), S. 135-142 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Short term memory ; Delayed matching to position ; 5-HT ; 5-HT1A receptor ; 8-OH DPAT ; Ipsapirone ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats. NAN-190 increased the latency to respond and reduced the number of nose pokes made during the delays in scopolamine-treated rats, and tended to potentiate the scopolamine-induced accuracy impairment. 1-PP did not affect the performance of scopolamine treated rats. Taken together, these results suggest that modulation of 5-HT1A receptors influences short term spatial working memory in the rat.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245055
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  • 139
    Digitale Medien
    Digitale Medien
    The neurosteroid pregnenolone sulfate blocks NMDA antagonist-induced deficits in a passive avoidance memory task (1994)
    Springer
    Psychopharmacology 116 (1994), S. 201-206 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Neurosteroid ; Memory ; Amnesia ; NMDA receptor ; Ataxia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The neurosteroid pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. In the present study, we examined the ability of PS to increase retention performance and to reduce deficits induced by a competitive NMDA receptor antagonist, the 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), in a step-through passive avoidance task in rats. Pretraining administration of PS (0.84–1680 pmol, ICV) had minimal effects on retention performance assessed 24 h after training, while CPP significantly decreased retention performance at the doses of 1.2 and 1.6 nmol (ICV). However, when administered in combination with CPP (1.2 nmol), PS (0.84–840 pmol, ICV) dose-dependently blocked the deficit in passive avoidance response induced by the NMDA antagonist. At the dose of 840 nmol, PS also significantly reduced the motor impairment induced by CPP (1.2 nmol). The blockade of CPP-induced behavioral deficits by PS may result from its positive modulatory action at NMDA receptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245063
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  • 140
    Digitale Medien
    Digitale Medien
    Dissociation between brown adipose tissue thermogenesis and sympathetic activity in rats with high plasma levels of oestradiol (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 40-43 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Brown adipose tissue ; Cold-acclimation ; Noradrenaline turnover ; Oestradiol ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract It has been shown previously that high plasma levels of oestradiol inhibit brown adipose tissue thermogenesis. Since rats and mice show a close association between thermogenic activity in and sympathetic discharge to brown fat, we measured the noradrenaline turnover in rats with high plasma levels of oestradiol to establish whether the observed inhibition of thermogenic activity is brought about by a reduction in the sympathetic drive to brown adipocytes. Oestradiol-filled Silastic capsules were implanted subcutaneously in female rats previously acclimated either to thermoneutrality or to cold. Control rats received empty implants. After 15 days treatment, noradrenaline turnover was measured by blocking its synthesis with α-methyl-p-tyrosine. As expected, noradrenaline turnover was higher in cold-acclimated rats than in rats kept at thermoneutrality. The presence of high plasma oestradiol levels did not alter sympathetic activity in any of the treated groups despite reducing thermogenic activity. This result reveals that oestradiol dissociates the thermogenic activity of brown adipose tissue from its sympathetic activation. Such dissociation has never been previously reported in rats, although it seems to be common in Syrian hamsters. However the causative factor in this species is unknown.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00374668
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  • 141
    Digitale Medien
    Digitale Medien
    Respiratory responses to combined hypoxia and hypothermia in rats after posterior hypothalamic lesions (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 371-377 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Body temperature ; Respiration ; Electrolytic lesions ; Urethrane anaesthesia ; Hypothalamus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (T bc) was maintained within the normal range (37–38° C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n=6) or posterior hypothalamus (n=6). Neither lesion altered respiration while rats breathed air at either T bc. At normal T bc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced T bc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00388299
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  • 142
    Digitale Medien
    Digitale Medien
    Effects of methionine sulphoximine treatment on renal amino acid and ammonia metabolism in rats (1994)
    Springer
    Pflügers Archiv 427 (1994), S. 524-532 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Glutamine synthetase ; Kidney ; Intestine ; Glutamine ; Ammonia ; Amino acids ; Metabolism ; Rat ; In vivo
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Renal glutamine metabolism in relation to ammoniagenesis has been extensively studied during chronic metabolic acidosis, when arterial glutamine levels are reduced. However, little is known about the effects of reduced glutamine delivery on renal glutamine and ammonia metabolism at physiological systemic pH values. Therefore, a model of decreased arterial glutamine concentrations at normal pH values was developed using methionine sulphoximine (MSO). Renal glutamine and ammonia metabolism was measured by determining fluxes and intracellular concentrations after an overnight fast in ether anaesthetized normal rats, MSO-treated rats and their pair-fed controls. Moreover, fluxes and intracellular concentrations of several other amino acids were determined concomitantly. After 2 and 4 days of MSO treatment, arterial glutamine concentrations were reduced to 55%, while arterial ammonia concentrations increased by 70%. Kidney glutamine uptake reduced, but systemic pH was unchanged. Fractional extraction of glutamine remained unchanged, suggesting that also in vivo net uptake of glutamine by the kidney at subnormal levels is related to arterial glutamine concentrations. As a result, at day 2 but not at day 4, the kidney reduced the net release of ammonia into the renal vein and thus reduced net renal ammonia addition to body ammonia pools. Therefore at day 2, the kidney seems to play an important role in adaptation to both hyperammonaemia and hypoglutaminaemia.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00374270
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  • 143
    Digitale Medien
    Digitale Medien
    Analysing ion channels with hidden Markov models (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 328-332 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Cortical collecting duct ; K+ channel ; Rat ; Isolated tubule ; Patch clamp
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ion channel current amplitudes (μ) and open probabilities (P o) have been analysed so far by defining a 50% threshold to distinguish between open and closed states of the channels. With this standard method (SM) it is very difficult or even impossible to analyse channels of different size in one membrane patch correctly. A stochastical model, named the hidden Markov model (HMM), separates between observation noise and the stochastic process of opening and closing of ion channels. The HMM allows the independent analysis of μ, P o, and mean dwell times (τ) of different channels in one membrane patch, without defining threshold levels. Using this method errors in the analysis are not summarized like in the SM because all different analysing procedures (e. g. filtering, setting of threshold, fitting processes) are done in one step. Two different K+ channels in excised basolateral membranes of the cortical collecting duct of rat (CCD) were analysed by the SM and the HMM. The μ value of the intermediate-conductance K+ channel (i-K+) was 3.9±0.1 pA (SM) and 3.8±0.2 pA (HMM) for 11 observations. The P o value of this channel was 10.2±4.2% (SM) and 10.1±4.0% (HMM). The mean τ values were 5.4±0.6 ms for the open state and 9.6±2.2 ms and 145±21 ms for the closed states (SM) and 7.8±1.1 ms, 7.7±0.9 ms and 148±24 ms (HMM), respectively. For seven small-conductance K+ (s-K+) channels, which were found in the same membrane patches as the i-K+, an accurate analysis of P o and τ was not possible with the SM. The μ value was 1.0±0.1 (SM), 0.9±0.1 (HMM) pA. P o was 16.6±4.6%, the open τ value was 11.1±2.8 ms, and the closed τ value was 34.9±8.5 ms. The HMM allows the analysis of single-channel currents, P o, and mean τ values when different or more than one ion channel(s) are colocalized in one membrane patch. Where analysis with the SM was possible results did not significantly differ from those obtained with the HMM. Thus for this kind of analysis the method of setting a 50% threshold appears justified.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00374789
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  • 144
    Digitale Medien
    Digitale Medien
    Oxygen consumption of oestradiol-treated rats (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 351-353 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Rat ; Brown adipose tissue ; Noradrenaline responsiveness ; Oxygen consumption ; Cold acclimation ; Body temperature ; Oxidative capacity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rectal temperature and oxygen consumption (üüO2) were monitored in female rats acclimated either to cold or to thermoneutrality and with and without chronic administration of oestradiol. The hormone is known to inactivate brown adipose tissue (BAT) and to reduce its response to noradrenaline (NA). The role of sympathetic control was studied by administering NA or the adrenergic blocker propranolol. Oestradiol treatment did not affect rectal temperature in the states of acclimation to thermoneutrality and to cold, nor did it change the hypothermic response of cold-exposed rats to temporary food deprivation. In the cold-acclimated rats, both controls and oestradiol-treated animals exhibited similar degrees of metabolic reduction after propranolol administration in the cold and similar degrees of metabolic activation by NA at thermoneutrality. Rats acclimated to thermoneutrality showed a larger metabolic response to NA when treated with oestradiol. The results suggest that oestradiol, while inactivating the BAT response to NA, activates the NA responsiveness of other metabolically active tissues in cold-induced thermogenesis. The observation of a greater oxidative capacity in the kidney and the rectus abdominis muscle of oestradiol-treated, cold-acclimated rats would be in line with this proposal.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00374793
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  • 145
    Digitale Medien
    Digitale Medien
    Alterations in the ontogeny of rat pup ultrasonic vocalization produced by prenatal exposure to nitrogen dioxide (1994)
    Springer
    Psychopharmacology 116 (1994), S. 423-427 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Nitrogen dioxide ; Prenatal exposure ; Behavior ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Wistar female rats were exposed to low concentrations of nitrogen dioxide, NO2 (1.5 and 3 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to this oxidant gas produced significant changes in the duration pattern of ultrasonic vocalizations emitted by male pups removed from their nest. In particular, a significant decrease in the length of ultrasonic calls was found in both 10- and 15-day-old rats exposed to NO2 (3 ppm) during gestation. These alterations were found at dose levels which did not significantly affect reproduction parameters, body weight gain and motor activity development. These findings suggest that gestational exposure to NO2, at concentrations below those associated with overt signs of toxicity, induces in rat offspring subtle behavioral changes characterized by altered ontogeny of ultrasonic emission.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02247472
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  • 146
    Digitale Medien
    Digitale Medien
    Sex-dimorphic psychomotor activation after perinatal exposure to (−)-Δ9-tetrahydrocannabinol. An ontogenic study in wistar rats (1994)
    Springer
    Psychopharmacology 116 (1994), S. 414-422 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Rat ; Development ; Δ-9-Tetrahydrocannabinol ; Motor behavior ; Locomotor activity ; Grooming ; Corticosterone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to Δ9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone. These results confirm our previous finding of a sex-dimorphic behavioral response to perinatal exposure to hashish extracts, and they suggest a role of THC-induced PA activation in the mediation of these actions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02247471
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  • 147
    Digitale Medien
    Digitale Medien
    Ontogeny of behavioral sensitization in the rat: effects of direct and indirect dopamine agonists (1994)
    Springer
    Psychopharmacology 116 (1994), S. 483-490 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Behavioral sensitization ; amphetamine ; NPA ; Ontogeny ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the present study, the abilities of NPA (a direct DA receptor agonist) and amphetamine (an indirect DA receptor agonist) to induce short- and long-term behavioral sensitization were assessed in 11- and 17-day-old rats (age at initial injection). Rats were injected on 4 consecutive days with amphetamine (1.0, 2.5, or 5.0 mg/kg), NPA (1.0 mg/kg), or saline. A final test day occurred either 2 days (experiment 1) or 8 days (experiment 2) later. On the test day, rats given successive agonist injections received a single injection of the same agonist again; whereas rats given successive saline injections received either amphetamine or NPA for the first time. Five minutes after injection, locomotor activity (line-crosses), stereotyped sniffing, and vertical activity were measured during a 30-min testing session. The results showed that 11- and 17-day-old rats exhibited behavioral sensitization when tested with NPA or amphetamine after a 2-day interval. In contrast, neither NPA nor amphetamine was able to sensitize the behaviors of preweanling rats when measured 8 days after initial drug treatments. Therefore, these results show that both direct and indirect DA agonists are able to induce short-term behavioral sensitization in preweanling rats, but that the mechanisms responsible for mediating long-term behavioral sensitization have not yet matured.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02247482
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  • 148
    Digitale Medien
    Digitale Medien
    Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam (1994)
    Springer
    Psychopharmacology 116 (1994), S. 475-482 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Stress ; Anxiety ; Rat ; Metabolism ; Energy expenditure ; Energy substrate utilisation ; Respiratory quotient ; Midazolam ; FG-7142 ; RO 15-1788 ; Panic ; Hyperventilation ; Sympathetic nervous system ; Benzodiazepine ; Conditioned stimulus ; Respiration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Changes in O2 consumption, CO2 production and locomotor activity were examined in rats exposed to (1) brief footshock, (2) an aversive conditioned stimulus (CS) predicting footshock, or (3) the anxiogenic drug FG-7142. Respiratory quotient (RQ=CO2 produced/O2 consumed) and energy expenditure [EE=O2 consumed (364+113RQ)] were derived to give an estimate of the energy substrate (fat, carbohydrate or protein) being utilised and total substrate oxidation respectively. In experiment 1, footshock (4 × 5 s 0.6 mA shocks over 2 min) produced an immediate increase in RQ, EE and activity. The RQ and EE effects were attenuated by the benzodiazepine midazolam (1 mg/kg). In experiment 2, an aversive CS, consisting of flashing light and buzzer that had 24 h earlier been repeatedly paired with footshock (20 × 5 s 0.6 mA shocks) caused a pronounced drop in RQ, an increase in EE and locomotor activity suppression. The effects of the aversive CS on RQ and EE were reversed by midazolam (1 mg/kg). In experiment 3, FG-7142 (10 mg/kg) produced a steep drop in RQ that persisted for at least 2 h and which was reversed by midazolam (1 mg/kg) and delayed by the benzodiazepine antagonist RO 15-1788 (10 mg/kg). FG-7142 also tended to inhibit EE and locomotor activity, but these effects did not reach statistical significance. Overall, these data show that stress causes profound alterations in RQ, EE and activity and that the pattern of change in these parameters differs with the nature of the stressor involved.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02247481
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  • 149
    Digitale Medien
    Digitale Medien
    Kavapyrone enriched extract fromPiper methysticum as modulator of the GABA binding site in different regions of rat brain (1994)
    Springer
    Psychopharmacology 116 (1994), S. 469-474 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Kavapyrone ; Piper methysticum ; GABA ; Rat ; Brain
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Regional differences in the modulation of [3H] muscimol binding to GABAA receptor complexes by kavapyrones, compounds of the rhizome of the plantPiper methysticum which possess sedative activity, were demonstrated using membrane fractions obtained from target brain centers of kavapyrone action: hippocampus (HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers outside the main kavapyrone effects as frontal cortex (FC) and cerebellum (CER). The kava extract enhanced the binding of [3H] muscimol in a concentration-dependent manner with maximal potentiation of 358% over control in HIP followed by AMY and MED (main target brain centers). Minimal stimulation was observed in CER followed by FC. In contrast, apart from CER, the potency of kavapyrones was similar in the brain areas investigated with EC50 values ranging between 200 and 300 µM kavapyrones. Scatchard analysis revealed that the observed effects of kavapyrones were due to an increase in the number of binding sites (Bmax), rather than to a change in affinity. At a kavapyrone concentration of 500 µM the order of enhancement in Bmax was HIP=AMY〉MED〉FC〉CER. When kavapyrones are included together with pentobarbital or HPO the two classes of compounds produced a more than additive, i.e., synergetic effect on [3H] muscimol binding. Our findings suggest that one way kavapyrones might mediate sedative effects in vivo is through effects on GABAA receptor binding.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02247480
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  • 150
    Digitale Medien
    Digitale Medien
    Excitatory amino acid receptors in the rostral ventrolateral medulla mediate hypertension induced by carotid body chemoreceptor stimulation (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 549-554 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Kynurenate ; Excitatory amino acid receptor ; Vasopressin ; Chemoreceptor ; Vasopressin antagonist ; Rostral ventrolateral medulla ; Carotid body ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The rostral ventrolateral medulla (RVLM) is involved in the mediation of cardiovascular responses to peripheral chemoreceptor stimulation. To investigate whether excitatory amino acid inputs in the RVLM are related to the responses to chemoreceptor stimulation, we microinjected kynurenate, an amino acid antagonist, unilaterally into the RVLM and examined its effects on the pressor response to stimulation of carotid body chemoreceptors. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The carotid chemoreceptors were stimulated with isotonic solutions of inorganic phosphate solution. Stimulation of carotid body chemoreceptors produced increases in blood pressure. Kynurenate injected ipsilaterally but not contralaterally into the RVLM markedly inhibited the pressor response to chemoreceptor stimulation. In rats with spinal transection, stimulation of carotid body chemoreceptors also produced increases in blood pressure. The pressor response in rats with spinal transection was inhibited by intravenous injection of a vasopressin antagonist or by kynurenate injected ipsilaterally into the RVLM. Kynurenate injected into the RVLM inhibited the pressor response to NMDA, AMPA and kainate but not to acetylcholine in intact rats. These findings indicate that excitatory amino acid receptors are involved in mediating the pressor response to carotid body chemoreceptor stimulation in the rat RVLM. It appears that the chemoreceptor stimulation produces an increase in vasopressin release and the enhancement of vasopressin release is also mediated by an increase in excitatory amino acid inputs in the RVLM.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01258457
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  • 151
    Digitale Medien
    Digitale Medien
    Halothane anesthesia enhances the effect of dopamine uptake inhibition on interstitial levels of striatal dopamine (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 239-244 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Halothane ; Vanoxerine ; GBR 12909 ; d-Amphetamine ; Dopamine uptake ; Microdialysis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The anesthetic, isoflurane, has been shown to potentiate the ability of the dopamine (DA)-uptake inhibitor, nomifensine, to increase the brain interstitial dopamine level ([DA]e). Since the effect of the more commenly used anesthetic, halothane, on this system is unknown, we determined [DA]e by microdialysis in the striatum of rats, conscious or anesthetized with halothane, in the presence of the more selective DA uptake inhibitor, vanoxerine (GBR 12909), or the DA releaser, d-amphetamine. Basal [DA]e was not changed by halothane. However, in halothane-anesthetized rats, the vanoxerine (3 mg/kg i.v.)-induced DA response increased severalfold compared to the response in conscious rats. The initial peak response to d-amphetamine (1 mg/kg i.v.) did not change, but the late response (1–3 h after injection) was augmented in anesthetized rats. Halothane is believed to increase firing of DA neurons in the substantia nigra and, hence, to release striatal DA. We hypothesize that [DA]e, is maintained at a normal level during the increased firing by equally increased activity of the DA transporter. However, when the DA transporter is blocked by vanoxerine, the increased DA release is unimpaired and [DA]e rises.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00175028
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  • 152
    Digitale Medien
    Digitale Medien
    Convulsant action of a benzodiazepine receptor agonist/inverse agonist Ro 19-4603 in developing rats (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 393-397 
    Details
    ISSN: 1432-1912
    Schlagwort(e): Seizures ; Development ; Rat ; Benzodiazepine ; Inverse agonist
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract An inverse benzodiazepine receptor agonist Ro 19-4603, administered intraperitoneally, was found to induce two types of motor seizures, i.e. minimal, predominantly clonic and major, generalized tonic-clonic, in rats at all developmental stages studied (7, 12, 18 and 25 days old). The developmental profile of the two types of seizure was different. Minimal seizures could be induced easily in the two youngest groups, whereas there were no marked differences in the induction of major seizures between the age groups. A lethal outcome was more common in 18- and 25-day-old rats than in younger animals. The convulsant action of the benzodiazepine agonist/inverse agonist Ro 19-4603 shows only quantitative changes during post-natal development in the rat.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00178957
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  • 153
    Digitale Medien
    Digitale Medien
    The AMPA antagonists NBQX and GYKI 52466 do not counteract neuroleptic-induced catalepsy (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 61-65 
    Details
    ISSN: 1432-1912
    Schlagwort(e): AMPA receptor ; NBQX ; GYKI 52466 ; Dizocilpine ; Quinpirole ; l-DOPA ; Catalepsy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The AMPA antagonists NBQX (2.5, 5, 10 mg/kg) and GYKI 52466 (4.8, 8 mg/kg) were investigated in haloperidol (0.5 mg/kg)-induced catalepsy in the rat. The effects of AMPA antagonists administered either alone or in combination with the noncompetitive NMDA antagonist dizocilpine (0.02 mg/kg), with the dopamine D-2 agonist quinpirole (1 mg/kg) or with L-DOPA (50, 100 mg/kg plus benserazide) were tested. NBQX or GYKI 52466 did not exert anticataleptic effects, neither alone nor in combination with dizocilpine, quinpirole or l-DOPA. Thus, in the rat inhibition of AMPA receptors with NBQX or GYKI 52466 does not have effects predictive for an antiparkinsonian potential.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00178207
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  • 154
    Digitale Medien
    Digitale Medien
    Expression of the α-subunit of glycoprotein hormones in the pars tuberalis-specific glandular cells in rat, mouse and guinea-pig (1994)
    Springer
    Cell & tissue research 278 (1994), S. 617-624 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Key words: Pituitary ; Pars tuberalis ; α-Subunit ; Immunocytochemistry ; In situ hybridization ; Rat ; Mouse ; Guinea-pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. The nature of the hormone(s) secreted by the pars tuberalis (PT) is still unknown. This pituitary lobe is mainly formed by specific glandular cells that differ in their ultrastructural features from the other adenohypophysial cell types. Data from the literature indicate the presence of thyroid-stimulating hormone immunoreactivity in the PT-specific cells of the rat and the Djungarian hamster but not of other species, including the mouse and guinea-pig. The PT also encloses variable numbers of pars distalis cells, essentially gonadotrophs that are mainly dispersed in its caudal area. We studied the expression of the glycoprotein hormone α-subunit in the PT of the rat, mouse and guinea-pig by in situ hybridization and immunocytochemistry. In situ hybridization, using an oligonucleotide probe complementary to rat cDNA sequence 196–237 revealed the expression of the α-subunit gene throughout the PT of the rat and the mouse; in the guinea-pig, the probe labelled no pituitary cells. Light- and electron-microscopic immunocytochemistry demonstrated α-subunit immunoreactivity in the secretory granules of the PT-specific cells in the three species examined. These cells did not react with a specific antibody against the β-subunit of luteinizing hormone, an antibody that labelled scattered gonadotrophs. The present data suggest that hormone(s) produced by the PT-specific glandular cells are, at least partly, related to glycoprotein hormones.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004410050253
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  • 155
    Digitale Medien
    Digitale Medien
    Expression of the α-subunit of glycoprotein hormones in the pars tuberalis-specific glandular cells in rat, mouse and guinea-pig (1994)
    Springer
    Cell & tissue research 278 (1994), S. 617-624 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Pituitary ; Pars tuberalis ; α-Subunit ; Immunocytochemistry ; In situ hybridization ; Rat ; Mouse ; Guinea-pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The nature of the hormone(s) secreted by the pars tuberalis (PT) is still unknown. This pituitary lobe is mainly formed by specific glandular cells that differ in their ultrastructural features from the other adenohypophysial cell types. Data from the literature indicate the presence of thyroid-stimulating hormone immunoreactivity in the PT-specific cells of the rat and the Djungarian hamster but not of other species, including the mouse and guinea-pig. The PT also encloses variable numbers of pars distalis cells, essentially gonadotrophs that are mainly dispersed in its caudal area. We studied the expression of the glycoprotein hormone α-subunit in the PT of the rat, mouse and guinea-pig by in situ hybridization and immunocytochemistry. In situ hybridization, using an oligonucleotide probe complementary to rat cDNA sequence 196–237 revealed the expression of the α-subunit gene throughout the PT of the rat and the mouse; in the guinea-pig, the probe labelled no pituitary cells. Light-and electron-microscopic immunocytochemistry demonstrated α-subunit immunoreactivity in the secretory granules of the PT-specific cells in the three species examined. These cells did not react with a specific antibody against the β-subunit of luteinizing hormone, an antibody that labelled scattered gonadotrops. The present data suggest that hormone(s) produced by the PT-specific glandular cells are, at least partly, related to glycoprotein hormones.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00331382
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  • 156
    Digitale Medien
    Digitale Medien
    The immunolocalization of small nuclear ribonucleoprotein particles in testicular cells during the cycle of the seminiferous epithelium of the adult rat (1994)
    Springer
    Cell & tissue research 278 (1994), S. 363-378 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Key words: snRNPs ; Testis ; Spermatocytes ; Spermatids ; Immunocytochemistry ; Chromatoid body ; Intermitochondrial nuage ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. The objective of this study was to determine the cellular and subcellular distribution of small nuclear ribonucleoprotein particles (snRNPs) in the adult rat testis in relation to the different cell types at the various stages of the cycle of the seminiferous epithelium. The distribution of snRNPs in the nucleus and cytoplasm of germ cells was quantitated in an attempt to correlate RNA processing with morphological and functional changes occurring during the development of these cells. Light-microscopic immunoperoxidase staining of rat testes with polyclonal anti-Sm and monoclonal anti-Y12 antibodies localized spliceosome snRNPs in the nuclei and cytoplasm of germ cells up to step 10 spermatids. Nuclear staining was intense in Sertoli cells, spermatogonia, spermatocytes, and in the early steps of round spermatid development. Although comparatively weaker, cytoplasmic staining for snRNPs was strongest in mid and late pachytene spermatocytes and early round spermatids. Quantitative electron-microscopic immunogold labeling of Lowicryl embedded testicular sections confirmed the light-microscopic observations but additionally showed that the snRNP content peaked in the cytoplasm of mid-pachytene spermatocytes and in the nuclei of late pachytene spermatocytes. The immunogold label tended to aggregate into distinct loci over the nuclear chromatin. The chromatoid body of spermatids and spermatocytes and the finely granular material in the interstices of mitochondrial aggregates of spermatocytes were found to be additional sites of snRNP localization and were intensely labeled. This colocalization suggests that these dense cytoplasmic structures may be functionally related. Anti-U1 snRNP antibodies applied to frozen sections showed the same LM localization pattern as spliceosome snRNPs. Anti-U3 snRNP antibodies applied to frozen sections stained nucleoli of germ cells where pre-rRNA is spliced.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00414179
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  • 157
    Digitale Medien
    Digitale Medien
    Selective association of nerve fibres immunoreactive for substance P or bombesin with putative cholinergic neurons of the male rat major pelvic ganglion (1994)
    Springer
    Cell & tissue research 278 (1994), S. 589-594 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Autonomic ganglia ; Neuropeptides ; Pelvic plexus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The male rat major pelvic ganglion contains both sympathetic and parasympathetic neurons that supply the lower urinary and digestive tracts, and the reproductive organs. The aim of this study was to describe the distribution and identify potential targets of sensory and intestinofugal axons in this ganglion. Two putative markers of these projections were chosen, substance P for primary sensory axons and bombesin for myenteric intestinofugal projections. Varicose substance P-immunoreactive axons were associated only with non-noradrenergic (putative cholinergic) somata, and most commonly with those that contained vasoactive intestinal peptide. Immunoreactivity for substance P was also present in a small group of non-noradrenergic somata, many of which were immunoreactive for enkephalins, neuropeptide Y or vasoactive intestinal peptide. Bombesin immunoreactivity was found only in preterminal and terminal (varicose) axons, the latter of which were exclusively associated with non-noradrenergic somata that contain neuropeptide Y-immunoreactivity. Some varicose axons containing either substance P-or bombesin-immunoreactivity were intermingled with clumps of small, intensely fluorescent cells. These studies indicate that substance P-and bombesin-immunoreactive axons are likely to connect with numerically small, but discrete, populations of pelvic neurons.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00331378
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  • 158
    Digitale Medien
    Digitale Medien
    Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study (1994)
    Springer
    Cell & tissue research 278 (1994), S. 21-28 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Key words: Adrenal cortex ; Renin-angiotensin system ; Steroidogenesis ; Electron microscopy ; Morphometry ; Rat ; transgenic (mRen2) 27
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00305774
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  • 159
    Digitale Medien
    Digitale Medien
    The immunolocalization of small nuclear ribonucleoprotein particles in testicular cells during the cycle of the seminiferous epithelium of the adult rat (1994)
    Springer
    Cell & tissue research 278 (1994), S. 363-378 
    Details
    ISSN: 1432-0878
    Schlagwort(e): snRNPs ; Testis ; Spermatocytes ; Spermatids ; Immunocytochemistry ; Chromatoid body ; Intermitochondrial nuage ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The objective of this study was to determine the cellular and subcellular distribution of small nuclear ribonucleoprotein particles (snRNPs) in the adult rat testis in relation to the different cell types at the various stages of the cycle of the seminiferous epithelium. The distribution of snRNPs in the nucleus and cytoplasm of germ cells was quantitated in an attempt to correlate RNA processing with morphological and functional changes occurring during the development of these cells. Light-microscopic immunoperoxidase staining of rat testes with polyclonal anti-Sm and monoclonal anti-Y12 antibodies localized spliceosome snRNPs in the nuclei and cytoplasm of germ cells up to step 10 spermatids. Nuclear staining was intense in Sertoli cells, spermatogonia, spermatocytes, and in the early steps of round spermatid development. Although comparatively weaker, cytoplasmic staining for snRNPs was strongest in mid and late pachytene spermatocytes and early round spermatids. Quantitative electron-microscopic immunogold labeling of Lowicryl embedded testicular sections confirmed the light-microscopic observations but additionally showed that the snRNP content peaked in the cytoplasm of midpachytene spermatocytes and in the nuclei of late pachytene spermatocytes. The immunogold label tended to aggregate into distinct loci over the nuclear chromatin. The chromatoid body of spermatids and spermatocytes and the finely granular material in the interstices of mitochondrial aggregates of spermatocytes were found to be additional sites of snRNP localization and were intensely labeled. This colocalization suggests that these dense cytoplasmic structures may be functionally related. Anti-U1 snRNP antibodies applied to frozen sections showed the same LM localization pattern as spliceosome snRNPs. Anti-U3 snRNP antibodies applied to frozen sections stained nucleoli of germ cells where pre-rRNA is spliced.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00414179
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  • 160
    Digitale Medien
    Digitale Medien
    Changes in fibre-type composition and myosin heavy-chain IId isoform in rat soleus muscle during recovery period after hindlimb suspension (1994)
    Springer
    European journal of applied physiology 68 (1994), S. 102-106 
    Details
    ISSN: 1439-6327
    Schlagwort(e): Hindlimb suspension ; Recovery ; Soleus muscle ; Fibre-type composition ; Myosin heavy-chain IId isoform ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We examined the changes in myosin heavy-chain (HC) isoforms and fibre-type composition in rat soleus muscle using both myosin adenosine triphosphatase staining and sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) analyses during the recovery period after 4 weeks of hindlimb suspension. Although there was no change in type IIc fibres after the suspension, an increase in this type of fibres was observed during the 1- to 4-week recovery period. The increase in type Ilc fibres was considered to be due to a shift from type Ila to IIc fibres. The SDS-PAGE analysis revealed the presence of the HC IId isoform, which was not observed in the control muscle, after a 4-week hindlimb suspension. The HC IId isoform gradually decreased over 3 weeks of recovery and disappeared in the 4th week of recovery after the suspension. These results suggest that the hypogravity conditions induced by hindlimb suspension stimulated the synthesis of the HC IId isoform, whereas an increase in mechanical load to the muscle accelerated the degradation of the HC IId isoform and the synthesis of type Ilc fibres during the recovery period after hindlimb suspension.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00599249
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  • 161
    Digitale Medien
    Digitale Medien
    Muscle glycogen repletion and pre-exercise glycogen content: effect of carbohydrate loading in rats previously fed a high fat diet (1994)
    Springer
    European journal of applied physiology 68 (1994), S. 483-488 
    Details
    ISSN: 1439-6327
    Schlagwort(e): Carbohydrate loading ; Glycogen utilization ; Glycogen repletion ; Glycogen synthase ; Muscle ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have recently reported that rates of muscle glycogen repletion during the early period of recovery were increased by carbohydrate (CHO) loading in rats previously fed a high fat diet. However, the reason for this remained unanswered. The purpose of this study was to examine whether an increase of glycogen utilization due to an elevated pre-exercise glycogen store would enhance rates of glycogen repletion in muscle. Despite an equal degree of glycogen depletion, the rates of glycogen repletion of soleus, red and white gastrocnemius muscles by postexercise administration of glucose (3.0 g · kg−1 body mass) and citrate (0.5 g · kg−1 body mass) were faster in the CHO loaded (3 days) rats than in the nonloaded rats, as a result of elevated pre-exercise glycogen content and consequently the greater glycogen utilization. The higher rate of muscle glycogen repletion may in part be explained by increased postexercise glycogen synthase activity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00599517
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  • 162
    Digitale Medien
    Digitale Medien
    Protein synthesis in the hippocampal slice: Transient inhibition by glutamate and lasting inhibition by ischemia (1994)
    Springer
    Metabolic brain disease 9 (1994), S. 235-247 
    Details
    ISSN: 1573-7365
    Schlagwort(e): Hippocampus ; Slices ; Protein synthesis ; Ischemia ; Glutamate ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Protein synthesis was measured in hippocampal slices which were exposed to glutamate (1 mM or 10 mM) or which were deprived of glucose and oxygen (‘in vitro ischemia’) for 15 min. Glutamate at 1 mM, a concentration estimated to occur duringin vivo ischemia did not affect protein synthesis. Ten mM glutamate inhibited protein synthesis immediately after exposure (50% of control values) and reduced ATP levels to about 30% of the control. After two hours, slices fully recovered their protein synthesis and energy metabolism. The effect of 10 mM glutamate was not receptor-mediated, as NMDA, AMPA, or metabotropic receptor antagonists failed to block the glutamate effect. Immediately after ischemia, protein synthesis was reduced to 30% of control values, and 2 hours later it was still depressed to one-half of control values. Energy charge, however, recovered completely. Ischemic inhibition of protein synthesis was not reversed by glutamate receptor antagonists. The data indicate that inhibition of protein synthesis in hippocampal slices during ischemia is not glutamate-dependent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01991197
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  • 163
    Digitale Medien
    Digitale Medien
    Experimental oxygen-induced retinal detachment in the newborn Wistar rat (1994)
    Springer
    Documenta ophthalmologica 87 (1994), S. 315-329 
    Details
    ISSN: 1573-2622
    Schlagwort(e): Experimental retinal detachment ; Glial fibrillary acidic protein ; Müller cells ; Oxygen ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We conducted an extensive histological study of the retinas of newborn rats that had been exposed to hyperoxic conditions. Our aim was to verify whether it is possible, using oxygen alone, to induce retinal detachment, a lesion that is characteristic of the more advanced stages of retinopathy of prematurity (ROP). Eight litters (total number of animals: 64) of newborn, albino Wistar rats were used. Four litters (32 rats) were exposed to 80% oxygen for the first ten days of life. Some of these rats were then removed to room-air environments where they were kept for two, three or four more weeks. The other four litters (32 rats) were maintained for the entire period in room-air. On the 11th, 25th, 32nd and 39th days of life rats from both the exposed and control groups were sacrificed and 5 micron sections of their in toto eyeballs were submitted to histological evaluation and immunohistochemical studies. Folding of the internal retinal layers was observed in some of the animals exposed to hyperoxia, as well as those kept in room air. These folds did not alter the overall thickness of the retina itself and were probably congenital. Retinal folds and microdetachments were seen in many of the retinas from the exposed group of rats. Extensive detachment was observed in one of the rats sacrificed after two weeks of room-air recovery, in two of those recovered for three weeks and in two exposed to four weeks of room air. The sections containing these areas of retinal detachment showed marked increases in glial fibrillary acidic protein (GFAP) in immunocytochemical studies, suggesting that Müller cells might play a role in the pathogenesis of retinal detachment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01203341
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  • 164
    Digitale Medien
    Digitale Medien
    Microvascular transfers of serratus anterior muscles in rats (1994)
    Springer
    European journal of plastic surgery 17 (1994), S. 1-4 
    Details
    ISSN: 1435-0130
    Schlagwort(e): Rat ; Free flaps ; Serratus anterior ; Microvascular surgery
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The serratus anterior muscle in the rat is supplied by the serratus division of thoracodorsal vessels, in a pattern similar to man [2]. The serratus anterior muscles were transferred to the groin area as a free muscle flap in 17 rats and as a free muscle graft in 13 rats. In the free muscle flap group, the serratus anterior muscles of 8 of 10 rats survived; histological examination showed them to be viable and the vascular anastomoses were patent at the 30th day. In the free muscle graft group, all of the muscle grafts became necrotic. As a result, it is concluded that the microvascular transfer of serratus anterior muscles in rats is a useful small animal model for microsurgical laboratory training of clinical free flap transfers and also for performing pharmacological and biochemical studies in transplanted muscle.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00176491
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  • 165
    Digitale Medien
    Digitale Medien
    The role of extracellular calcium in pregnancy-induced attenuation of phenylephrine contraction in rat aorta with functional endothelium (1994)
    Springer
    Journal of comparative physiology 164 (1994), S. 81-87 
    Details
    ISSN: 1432-136X
    Schlagwort(e): Vascular smooth muscle ; Phenylephrine-induced contraction ; Pregnancy ; Aorta ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The effect of pregnancy on the supply of calcium ions for the contractile responses of rat aortic rings to phenylephrine was investigated. The contractility of intact aortic rings from pregnant rats, compared with that of similar rings from non-pregnant rats, to phenylephrine and potassium chloride was significantly decreased. Contractions of rings from non-pregnant rats, pretreated with phenylephrine or potassium chloride, in response to calcium chloride were greater than those of similarly treated rings from pregnant rats. When the concentration of calcium chloride in the medium bathing the rings was reduced to 0.8 mmol·l-1, the contractile response to phenylephrine was significantly (P〈0.005) inhibited in rings from both pregnant and non-pregnant rats but to a greater extent in rings from non-pregnant rats. Contractions of aortic rings from pregnant rats in response to phenylephrine in calcium-free medium were similar to those of rings from non-pregnant rats, suggesting equal dependence on calcium from intracellular stores. The results suggest that pregnancy decreased the response to calcium influx into the aortic smooth muscle cells through both receptor-and voltage-operated calcium entry pathways. Since de-endothelialisation reversed the pregnancy-induced diminished contraction to phenylephrine, it is likely that pregnancy interferred with contractions induced by activation of receptors with phenylephrine through enhanced production of endothelium-derived relaxing factor(s).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00714575
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  • 166
    Digitale Medien
    Digitale Medien
    Solution structure of a core peptide derived from scyllatoxin (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 205-215 
    Details
    ISSN: 0887-3585
    Schlagwort(e): peptide folding ; disulfide framework ; insect toxins ; NMR ; distance geometry ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: An analysis of the sequences of scyllatoxin and charybdotoxin suggested that it would be possible to design a core peptide sequence which would still fold to give the β-hairpin and helix seen in the toxins, but which would eliminate one disulfide and connecting residues. The core sequence was modeled, then synthesized and purified. The cysteines oxidize in air to give the same disulfide pairings as seen in the parent toxins as the major product. The three-dimensional structure of the core sequence peptide, termed Max, was determined using proton NMR spectroscopy and found to be identical in secondary structure to the toxins. However differences were found in the relative orientation of the β-hairpin and helix. The use of this structural motif, found in many insect toxins, as a disulfide framework for exploring sequence/structure/activity relationships is discussed. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180302
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  • 167
    Digitale Medien
    Digitale Medien
    Thermodynamics of ubiquitin unfolding (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 246-253 
    Details
    ISSN: 0887-3585
    Schlagwort(e): microcalorimetry ; heat capacity ; enthalpy ; hydrogen bonding ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The energetics of ubiquitin unfolding have been studied using differential scanning microcalorimetry. For the first time it has been shown directly that the enthalpy of protein unfolding is a nonlinear function of temperature. Thermodynamic parameters of ubiquitin unfolding were correlated with the structure of the protein. The enthalpy of hydrogen bonding in ubiquitin was calculated and compared to that obtained for other proteins. It appears that the energy of hydrogen bonding correlates with the average length of the hydrogen bond in a given protein structure. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180305
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  • 168
    Digitale Medien
    Digitale Medien
    Hydrogen bond strength and β-sheet propensities: The role of a side chain blocking effect (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 262-266 
    Details
    ISSN: 0887-3585
    Schlagwort(e): protein structure prediction ; protein stability ; hydrogen bond ; β-sheet ; amino acid propensity ; steric effect ; hydrogen exchange ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Amino acid side chains can enhance peptide group hydrogen bond strength in protein structures by obstructing the competing hydrogen bond to solvent in the unfolded state. Available data indicate that the steric blocking effect contributes an average of 0.5 kJ per residue to protein hydrogen bond strength and accounts for the intrinsic α-sheet propensities of the amino acids. In available data for helical models, the contribution to α-helix propensities is obscured especially by large context-dependent effects. These issues are all related by a common side chain-dependent steric clash which disfavors peptide to water H-bond formation, peptide to catalyst complexation in hydrogen exchange reactions (Bai et al., Proteins 17:75-86, 1993), and peptide to peptide H-bonding in the helical main chain conformation (Creamer and Rose, Proc. Natl. Acad. Sci. U.S.A. 89:5937-5941, 1992) but not in α-strands. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180307
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  • 169
    Digitale Medien
    Digitale Medien
    A method for α-helical integral membrane protein fold prediction (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 281-294 
    Details
    ISSN: 0887-3585
    Schlagwort(e): membrane ; protein ; structure ; prediction ; G-protein coupled receptor ; rhodopsin ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Integral membrane proteins (of the α-helical class) are of central importance in a wide variety of vital cellular functions. Despite considerable effort on methods to predict the location of the helices, little attention has been directed toward developing an automatic method to pack the helices together. In principle, the prediction of membrane proteins should be easier than the prediction of globular proteins: there is only one type of secondary structure and all helices pack with a common alignment across the membrane. This allows all possible structures to be represented on a simple lattice and exhaustively enumerated. Prediction success lies not in generating many possible folds but in recognizing which corresponds to the native. Our evaluation of each fold is based on how well the exposed surface predicted from a multiple sequence alignment fits its allocated position. Just as exposure to solvent in globular proteins can be predicted from sequence variation, so exposure to lipid can be recognized by variable-hydrophobic (variphobic) positions. Application to both bacteriorhodopsin and the eukaryotic rhodopsin/opsin families revealed that the angular size of the lipid-exposed faces must be predicted accurately to allow selection of the correct fold. With the inherent uncertainties in helix prediction and parameter choice, this accuracy could not be guaranteed but the correct fold was typically found in the top six candidates. Our method provides the first completely automatic method that can proceed from a scan of the protein sequence databanks to a predicted three-dimensional structure with no intervention required from the investigator. Within the limited domain of the seven helix bundle proteins, a good chance can be given of selecting the correct structure. However, the limited number of sequences available with a corresponding known structure makes further characterization of the method difficult. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180309
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  • 170
    Digitale Medien
    Digitale Medien
    Crystallization and preliminary crystallographic studies of the precursor and mature forms of a neutral lipase from the fungus Rhizopus delemar (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 301-306 
    Details
    ISSN: 0887-3585
    Schlagwort(e): triglyceride lipase ; proenzyme ; molecular replacement ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: A neutral lipase from the filamentous fungus Rhizopus delemar has been crystallized in both its proenzyme and mature forms. Although the latter crystallizes readily and produces a variety of crystal forms, only one was found to be suitable for X-ray studies. It is monoclinic (C2, a = 92.8 Å, b = 128.9 Å, c = 78.3 Å, β = 135.8) with two molecules in the asymmetric unit related by a noncrystallographic diad. The prolipase crystals are orthorhombic (P212121, with a = 79.8 Å, b = 115.2 Å, c = 73.0 Å) and also contain a pair of molecules in the asymmetric unit. Initial results of molecular replacement calculations using the refined coordinates of the related lipase from Rhizomucor miehei identified the correct orientations and positions of the protein molecules in the unit cells of crystals of both proenzyme and the mature form. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180311
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  • 171
    Digitale Medien
    Digitale Medien
    Correlated mutations and residue contacts in proteins (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 309-317 
    Details
    ISSN: 0887-3585
    Schlagwort(e): protein structure prediction ; predicted contact maps ; correlated mutations ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The maintenance of protein function and structure constrains the evolution of amino acid sequences. This fact can be exploited to interpret correlated mutations observed in a sequence family as an indication of probable physical contact in three dimensions. Here we present a simple and general method to analyze correlations in mutational behavior between different positions in a multiple sequence alignment. We then use these correlations to predict contact maps for each of 11 protein families and compare the result with the contacts determined by crystallography. For the most strongly correlated residue pairs predicted to be in contact, the prediction accuracy ranges from 37 to 68% and the improvement ratio relative to a random prediction from 1.4 to 5.1. Predicted contact maps can be used as input for the calculation of protein tertiary structure, either from sequence information alone or in combination with experimental information. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180402
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  • 172
    Digitale Medien
    Digitale Medien
    Analysis of Cα geometry in protein structures (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 324-337 
    Details
    ISSN: 0887-3585
    Schlagwort(e): protein structure ; secondary structure ; peptide geometry ; Ramachandran plot ; β-turns ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The polypeptide of a protein molecule can be considered as a chain of Cα atoms linked by pseudobonds between the Cα atoms of successive amino acid residues. This paper presents an analysis of the angle and dihedral angles made by these pseudobonds in protein structures determined at high resolution by X-ray crystallography. This analysis reveals a strong correlation between Cα geometry and the protein fold. The regular features of protein secondary structure such as α-helix and α-sheet are very clearly defined. In addition, it is possible to identify with some confidence the discrete populations of particular conformations of α-turn. Comparison with the traditional Ramachandran type of plot demonstrates that an analysis of protein structure on the basis of Cα geometry provides a richer description of protein conformation. In addition, the characteristics of this geometry could be a useful guide in model building of protein structure. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180404
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  • 173
    Digitale Medien
    Digitale Medien
    Crystallization of a fragment of human fibronectin: Introduction of methionine by site-directed mutagenesis to allow phasing via selenomethionine (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 48-54 
    Details
    ISSN: 0887-3585
    Schlagwort(e): X-ray crystallography ; extracellular matrix ; multiwavelength anomalous diffraction (MAD) ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Crystals of a fragment of human fibronectin encompassing the 7th through the RGD-containing 10th type III repeats (FN7-10) have been produced with protein expressed in E. coli. The crystals are monoclinic with one molecule in the asymmetric unit and diffract to beyond 2.0 Å Bragg spacings. A mutant FN7-10 was produced in which three methionines, in addition to the single native methionine already present, have been introduced by site-directed mutagenesis. Diffraction-quality crystals of this mutant protein have been grown in which methionine was replaced with selenomethionine. The introduction of methionine by site-directed mutagenesis to allow phasing from selenomethionyl-substituted crystals is shown to be feasible by this example and is proposed as a general approach to solving the crystallographic phase problem. Strategies for selecting propitious sites for methionine mutations are discussed. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190107
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  • 174
    Digitale Medien
    Digitale Medien
    Combining evolutionary information and neural networks to predict protein secondary structure (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 55-72 
    Details
    ISSN: 0887-3585
    Schlagwort(e): secondary structure prediction ; prediction of secondary structure class ; prediction of secondary structure content ; evolutionary information ; multiple alignment profiles ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Using evolutionary information contained in multiple sequence alignments as input to neural networks, secondary structure can be predicted at significantly increased accuracy. Here, we extend our previous three-level system of neural networks by using additional input information derived from multiple alignments. Using a position-specific conservation weight as part of the input increases performance. Using the number of insertions and deletions reduces the tendency for overprediction and increases overall accuracy. Addition of the global amino acid content yields a further improvement, mainly in predicting structural class. The final network system has a sustained overall accuracy of 71.6% in a multiple cross-validation test on 126 unique protein chains. A test on a new set of 124 recently solved protein structures that have no significant sequence similarity to the learning set confirms the high level of accuracy. The average cross-validated accuracy for all 250 sequence-unique chains is above 72%. Using various data sets, the method is compared to alternative prediction methods, some of which also use multiple alignments: the performance advantage of the network system is at least 6 percentage points in three-state accuracy. In addition, the network estimates secondary structure content from multiple sequence alignments about as well as circular dichroism spectroscopy on a single protein and classifies 75% of the 250 proteins correctly into one of four protein structural classes. Of particular practical importance is the definition of a position-specific reliability index. For 40% of all residues the method has a sustained three-state accuracy of 88%, as high as the overall average for homology modelling. A further strength of the method is greatly increased accuracy in predicting the placement of secondary structure segments. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190108
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  • 175
    Digitale Medien
    Digitale Medien
    Expression, purification, and crystallization of restriction endonuclease PvuII with DNA containing its recognition site (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 77-79 
    Details
    ISSN: 0887-3585
    Schlagwort(e): endonuclease overexpression ; crystallization ; X-ray diffraction ; protein-DNA complex ; Type II restriction enzyme ; vapor diffusion ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: We have overexpressed the type II restriction endonuclease PvuII (R.PvuII) in E. coli, prepared large amounts of the homogeneous enzyme, and crystallized it with an oligonucleotide carrying a PvuII recognition site. The cocrystals are orthorhombic space group P212121 with cell constants a = 95.8 Å, b = 86.3 Å, c = 48.5 Å, and diffract X-rays to at least 2.7 Å. There is a complex of two protein subunits and one oligonucleotide duplex in the asymmetric unit. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190110
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  • 176
    Digitale Medien
    Digitale Medien
    Masthead (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994) 
    Details
    ISSN: 0887-3585
    Schlagwort(e): Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190201
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  • 177
    Digitale Medien
    Digitale Medien
    Crystallization and preliminary X-ray crystallographic analysis of phospholipid transfer protein from maize seedlings (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 80-83 
    Details
    ISSN: 0887-3585
    Schlagwort(e): maize protein ; crystals ; X-ray diffraction ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Phospholipid transfer protein from maize seedlings has been crystallized using trisodium citrate as precipitant. The crystal belongs to the orthorhombic space group P212121 with unit cell dimensions of a = 24.46 Å, b = 49.97 Å, and c = 69.99 Å. The presence of one molecule in the asymmetric unit gives a crystal volume per protein mass (Vm) of 2.36 Å 3/Da and a solvent content of 48% by volume. The X-ray diffraction pattern extends at least to 1.6 Å Bragg spacing when exposed to both CuKα and synchrotron X-rays. A set of X-ray data to approximately 1.9 Å Bragg spacing has been collected from a native crystal. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190111
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  • 178
    Digitale Medien
    Digitale Medien
    α-Helix-forming propensities in peptides and proteins (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 85-97 
    Details
    ISSN: 0887-3585
    Schlagwort(e): protein conformation ; secondary structure ; protein folding ; helix stability ; helix formation ; conformational entropy ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Much effort has been invested in seeking to understand the thermodynamic basis of helix stability in both peptides and proteins. Recently, several groups have measured the helix-forming propensities of individual residues (Lyu, P. C., Liff, M. I., Marky, L. A., Kallenbach, N. R. Science 250:669-673, 1990; O'Neil, K. T., DeGrado, W. F. Science 250:646-651, 1990; Padmanabhan, S., Marqusee, S., Ridgeway, T., Laue, T. M., Baldwin, R. L. Nature (London) 344:268-270, 1990). Using Monte Carlo computer simulations, we tested the hypothesis that these differences in measured helix-forming propensity are due primarily to loss of side chain conformational entropy upon helix formation (Creamer, T. P., Rose, G. D. Proc. Natl. Acad. Sci. U.S.A. 89:5937-5941, 1992). Our previous study employed a rigid helix backbone, which is here generalized to a completely flexible helix model in order to ensure that earlier results were not a methodological artifact. Using this flexible model, side chain rotamer distributions and entropy losses are calculated and shown to agree with those obtained earlier. We note that the side chain conformational entropy calculated for Trp in our previous study was in error; a corrected value is presented. Extending earlier work, calculated entropy losses are found to correlate strongly with recent helix propensity scales derived from substitutions made within protein helices (Horovitz, A., Matthews, J. M., Fersht, A. R. J. Mol. Biol. 227:560-568, 1992; Blaber, M., Zhang, X.-J., Matthews, B. M. Science 260:1637-1640, 1993). In contrast, little correlation is found between these helix propensity scales and the accessible surface area buried upon formation of a model polyalanyl α-helix. Taken in sum, our results indicate that loss of side chain entropy is a major determinant of the helix-forming tendency of residues in both peptide and protein helices. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190202
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  • 179
    Digitale Medien
    Digitale Medien
    1.56 Å structure of mature truncated human fibroblast collagenase (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 98-109 
    Details
    ISSN: 0887-3585
    Schlagwort(e): crystallography ; hydroxamate ; high resolution ; metalloproteinase ; zinc ; X-ray ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The X-ray crystal structure of a 19 kDa active fragment of human fibroblast collagenase has been determined by the multiple isomorphous replacement method and refined at 1.56 Å resolution to an R-factor of 17.4%. The current structure includes a bound hydroxamate inhibitor, 88 waters and three metal atoms (two zincs and a calcium). The overall topology of the enzyme, comprised of a five stranded β-sheet and three α-helices, is similar to the thermolysin-like metalloproteinases. There are some important differences between the collagenase and thermolysin families of enzymes. The active site zinc ligands are all histidines (His-218, His-222, and His-228). The presence of a second zinc ion in a structural role is a unique feature of the matrix metalloproteinases. The binding properties of the active site cleft are more dependent on the main chain conformation of the enzyme (and substrate) compared with thermolysin. A mechanism of action for peptide cleavage similar to that of thermolysin is proposed for fibroblast collagenase. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 11 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190203
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  • 180
    Digitale Medien
    Digitale Medien
    Kinetic study on myoglobin refolding monitored by five optical probe stopped-flow methods (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 110-119 
    Details
    ISSN: 0887-3585
    Schlagwort(e): folding intermediate ; urea denaturation ; stopped-flow circular dichroism ; molten globule ; hemindicyanide ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The refolding kinetics of horse cyanometmyoglobin induced by concentration jump of urea was investigated by five optical probe stopped-flow methods: absorption at 422 nm, tryptophyl fluorescence at around 340 nm, circular dichroism (CD) at 222 nm, CD at 260 nm, and CD at 422 nm. In the refolding process, we detected three phases with rate constants of 〉 1 × 102 s-1, (4.5-9.3) S-1, and (2-5) × 10-3 s-1. In the fastest phase, a substantial amount of secondary structure (40%) is formed within the dead time of the CD stopped-flow apparatus (10.7 ms). The kinetic intermediate populated in the fastest phase is shown to capture a hemindicyanide, suggesting that a “heme pocket precursor” recognized by hemindicyanide must be constructed within the dead time. In the middle phase, most of secondary and tertiary structures, especially around the captured hemindicyanide, have been constructed. In the slowest phase, we detected a minor structural rearrangement accompanying the ligand-exchange reaction in the fifth coordination of ferric iron. We present a possible model for the refolding process of myoglobin in the presence of the heme group. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190204
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  • 181
    Digitale Medien
    Digitale Medien
    Decoupling of melting domains in immobilized ribonuclease A (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 120-131 
    Details
    ISSN: 0887-3585
    Schlagwort(e): enzymes ; protein immobilization ; microcalorimetry ; protein melting domains ; protein DSC ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Ribonuclease A has been immobilized on silica beads through glutaraldeyde-mediated chemical coupling in order to improve the stability of the protein against thermal denaturation. The thermodynamic and binding properties of the immobilized enzyme have been studied and compared with those of the free enzyme. The parameters describing the binding of the inhibitor 3′ -CMP (Ka and ΔH) as monitored by spectrophotometry and calorimetry were not significantly affected after immobilization. Conversely both the stability and unfolding mechanism drastically changed. Thermodynamic analysis of the DSC data suggests that uncoupling of protein domains has occurred as a consequence of the immobilization. The two state approximation of the protein unfolding process is not longer valid for the immobilized RNase. Protein stability strongly depends on the hydrophobicity properties of the support surface as well as on the presence of the inhibitor and pH. For example, after immobilization on a highly hydrophobic surface, the enzyme is partially in the unfolded state. The binding of a ligand is able to reorganize the protein structure into a native-like conformation. The refolding rates are different for the two protein domains and vary as a function of pH and presence of the inhibitor 3′-CMP. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190205
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  • 182
    Digitale Medien
    Digitale Medien
    Temperature-induced complementarity as a mechanism for biomolecular assembly (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 73-76 
    Details
    ISSN: 0887-3585
    Schlagwort(e): molecular recognition ; protein assembly ; protein folding ; protein interactions ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Recent advances in the measurement and theory of “hydration” interactions between biomolecules provide a basis on which to formulate mechanisms of biomolecular recognition. In this paper we have developed a mathematical formalism for analyzing specificity encoded in dynamic distributions of surface polar groups, a formalism that incorporates newly recognized properties of directly measured “hydration” forces. As expected, attraction between surfaces requires complementary patterns of surface polar groups. In contrast to usual expectations, thermal motion can create these complementary surface configurations. We have demonstrated that assembly can occur with an increase in conformational entropy of polar residues. Elevated temperature then facilitates recognition rather than hinders it. This mechanism might underlie some temperature-favored assembly reactions common in biological systems that are usually associated with the “hydrophobic effect” only. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190109
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  • 183
    Digitale Medien
    Digitale Medien
    Coiled-coil stutter and link segments in keratin and other intermediate filament molecules: A computer modeling study (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 174-184 
    Details
    ISSN: 0887-3585
    Schlagwort(e): coiled-coils ; keratin ; intermediate filament proteins ; link segments ; heptad phasing ; computer modeling ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Structural discontinuities have previously been identified in four regions of the coiled-coil rod domain structure present in intermediate filament (IF) protein molecules. These include a point at which a phase shift occurs in the heptad periodicity characteristic of the sequence of polar and apolar residues in α-helical coiled-coils, and three links that lack a heptad substructure. We have studied these regions by computer-based molecular modeling and comparative sequence analysis and conclude that the phasing discontinuity can be accommodated without significant distortion of the overall double-helical chain conformation; the L2 link has a similar conformation in all different types of IF molecules, a favorable conformation being one in which the two strands wrap tightly around each other; the L12 links vary in length between different IF types but contain important sequence similarities suggestive of a partial β structure; the L1 links show larger variations in length, a lower degree of similarity, and probably diverse structures. Variations in the overall charges of the different links suggest that ionic interactions may playa significant role in filament assembly. The results also have general significance for other α-fibrous proteins in which either the characteristic heptad phasing undergoes a discontinuity or where a short non-coiled-coil sequence occurs within a coiled-coil rod domain structure. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200207
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  • 184
    Digitale Medien
    Digitale Medien
    Crystallization and characterization of the recombinant human Clara cell 10-kDa protein (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 191-196 
    Details
    ISSN: 0887-3585
    Schlagwort(e): human Clara cell 10-kDa protein ; X-ray diffraction ; phospholipase A2 inhibitor ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Crystals of recombinant human Clara cell 10-kDa protein were grown both from ammonium sulfate and polyethylene glycol (PEG) solutions. Crystals grown from ammonium sulfate solution have been characterized by X-ray diffraction studies as monoclinic with the space group C2 and lattice constants a = 69.2 Å, b = 83.0 Å, c = 58.3 Å, and β = 99.7°. The monoclinic crystals diffract to beyond 2.5 Å. Some of the crystals grown from PEG were of a similar habit to those grown from ammonium sulfate, but others were triclinic with the space group P1 and cell constants a = 40.3 Å, b = 46.3 Å, c = 51.3 Å, α = 117.7°, β = 102.3°, and γ = 71.4°. These crystals diffract to beyond 3.2 Å. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200209
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  • 185
    Digitale Medien
    Digitale Medien
    Conformational analysis of hemopexin by fourier-transform infrared and circular dichroism spectroscopy (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 185-190 
    Details
    ISSN: 0887-3585
    Schlagwort(e): heme ; secondary structure ; conformation ; hemopexin ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Hemopexin is a serum glyco-protein that binds heme with the highest known affinity of any characterized heme-binding protein and plays an important role in receptormediated cellular heme uptake. Complete understanding of the function of hemopexin will require the elucidation of its molecular structure. Previous analysis of the secondary structure of hemopexin by far-UV circular dichroism (CD) failed due to the unusual positive ellipticity of this protein at 233 nm. In this paper, we present an examination of the structure of hemopexin by both Fourier-transform infrared (FTIR) and circular dichroism spectroscopy. Our studies show that hemopexin contains about 55% β-structure, 15% α-helix, and 20% turns. The two isolated structural domains of hemopexin each have secondary structures similar to hemopexin. Although there are significant tertiary conformational changes indicated by the CD spectra, the overall secondary structure of hemopexin is not affected by binding heme. However, moderate changes in secondary structure do occur when the heme-binding domain of hemopexin associates with heme. In spite of the exceptionally tight binding at neutral pH, heme is released from the bis-histidyl heme-hemopexin complex at pH 5.0. Under this acidic condition, hemopexin maintains the same overall secondary structure as the native protein and is able to resume the heme-binding function and the native structure of the hemeprotein (as indicated by the CD spectra) when returned to neutral pH. We propose that the state of hemopexin identified in vitro at pH 5.0 resembles that of this protein in the acidic environment of the endosomes in vivo when hemopexin releases heme during receptor-mediated endocytosis. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200208
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  • 186
    Digitale Medien
    Digitale Medien
    Masthead (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994) 
    Details
    ISSN: 0887-3585
    Schlagwort(e): Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200301
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  • 187
    Digitale Medien
    Digitale Medien
    Preliminary crystallographic analysis of an enzyme involved in erythromycin biosynthesis: Cytochrome P450eryF (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 197-201 
    Details
    ISSN: 0887-3585
    Schlagwort(e): cytochrome P450 ; erythromycin ; P450eryF ; crystallization ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Cytochrome P450eryF was overexpressed in Escherichia coli and purified in high yield. Crystals of the protein in the presence of the substrate, 6-deoxyerythronolide B, have been obtained by the hanging drop vapor diffusion method, using polyethylene glycol 4000 as a precipitant. The crystals belong to the orthorhombic space group P212121 with unit cell dimensions of a = 54.16 Å, b = 79.67 Å, and c = 99.48 Å and one molecule per asymmetric unit. A complete native data set has been collected to a resolution of 2.1 Å, and anomalous dispersion difference Patterson maps have revealed the location of the single heme iron atom. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200210
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  • 188
    Digitale Medien
    Digitale Medien
    Homology modeling of the Abl-SH3 domain (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 203-215 
    Details
    ISSN: 0887-3585
    Schlagwort(e): SH3 ; Abl ; molecular modeling ; homology modeling ; molecular dynamics ; protein structure prediction ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: A tertiary structure model of the Abl-SH3 domain is predicted by using homology modeling techniques coupled to molecular dynamics simulations. Two template proteins were used, Fyn-SH3 and Spc-SH3. The refined model was extensively checked for errors using criteria based on stereochemistry, packing, solvation free-energy, accessible surface areas, and contact analyses. The different checking methods do not totally agree, as each one evaluates a different characteristic of protein structures. Several zones of the protein are more susceptible to incorporating errors. These include residues 13, 15, 35, 39, 45, 46, 50, and 60. An interesting finding is that the measurement of the Cα chirality correlated well with the rest of the criteria, suggesting that this parameter might be a good indicator of correct local conformation. Deviations of more than 4 degrees may be indicative of poor local structure. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200302
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  • 189
    Digitale Medien
    Digitale Medien
    Homologous modeling of the lysosomal protective protein/carboxypeptidase L: Structural and functional implications of mutations identified in galactosialidosis patients (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 81-93 
    Details
    ISSN: 0887-3585
    Schlagwort(e): serine carboxypeptidase ; protein modeling ; mutation analysis ; comparative modeling ; cathepsin A ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The deficiency of the lysosomal protective protein/carboxypeptidase L (CARB L) causes the lysosomal storage disorder, galactosialidosis, characterized by neuraminidase and β-galactosidase deficiencies in patients' cells. The three enzymes form a complex inside the lysosome, and the neuraminidase and β-galactosidase deficiencies are secondary to CARB L deficiency. Sequence similarity and common enzymological properties suggest that the protomeric tertiary structure of CARB L is conserved within a family of serine carboxypeptidases which includes the yeast carboxypeptidase Y, killer expression I gene product and several plant carboxypeptidases. We used this homology to build a model of the CARB L structure based on the recently published X-ray atomic coordinates of the wheat carboxypeptidase II (CPDW-II) which shares 32% primary structure identity with CARB L. Small insertions and deletions were accommodated into the model structure by energy minimization using the DREIDING II force field. The Cα atomic-coordinates of the final CARB L model have a RMS shift of 1.01 Å compared to the corresponding conserved residues in the CPDW-II template structure. The correct orientation of the homologous catalytic triad residues Ser150, His429 and Asp392, the potential energy calculations and the distribution of hydrophobic and hydrophillic residues in the structure all support the validity of the CARB L model. Most missense mutations identified in galactosialidosis patients were located in secondary structural elements except for the Tyr211→Asn mutation which is in a loop. The other mutant residues have their side chains deeply buried in the central β-sheet of the model structure except for the Phe412→Val mutation which is located in the dimer interface. The predicted effects of specific mutations on CARB L structural stability correlates well with recently published transient expression studies of mutant CARB L (Shimmoto, M. et al., J. Clin. Invest., 91:2393-2399, 1993). © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180110
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  • 190
    Digitale Medien
    Digitale Medien
    Protein simulations using techniques suitable for very large systems: The cell multipole method for nonbond interactions and the Newton-Euler inverse mass operator method for internal coordinate dynamics (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 227-247 
    Details
    ISSN: 0887-3585
    Schlagwort(e): cell multipole method ; Newton-Euler inverse mass operator ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Two new methods developed for molecular dynamics simulations of very large proteins are applied to a series of proteins ranging up to the protein capsid of tomato bushy stunt virus (TBSV).For molecular dynamics of very large proteins and polymers, it is useful to carry out the dynamics using internal coordinates (say, torsions only) rather than Cartesian coordinates. This allows larger time steps, eliminates problems with the classical description of high energy modes, and focuses on the important degrees of freedom. The resulting equation of motion has the form where for T is the vector of generalized forces, M(θ) is the moments of inertia tensor, is the vector of torsions, and C is a vector containing Coriolis forces and nonbond forces. The problem is that to calculate the acceleration vector from M, C, and Trequires inverting. M(θ), an order N3calculation. Since the number of degrees of freedom might be 300,000 for a million atom system, solving these equations every time step is impractical, restricting internal coordinate methods to small systems. The new method, Newton-Euler Inverse Mass Operator (NEIMO) dynamics, constructs the torsional accelerations vector directly by an order N process, allowing internal-coordinate dynamics to be solved for super larger (million atom) systems, The first use of the NEIMO method for molecular dynamics of proteins is presented here.A second serious difficulty for large proteins is calculation of the nonbond forces. We report here the first application to proteins of the new Cell Multipole Method (CMM) to evaluate the Coulomb and van der Waals interactions. The cost of CMM scales linearly with the number of particles while retaining an accuracy significantly better than standard non bond methods (involving cutoffs).Results for NEIMO and CMM are given for simulations of a wide range of peptide and protein systems, including the protein capsid of TBSV with 488,000 atoms. The computational times for NEIMO and CMM are demonstrated to scale linearly with size. With NEIMO the dynamics time steps can be as large as 20 fs (for small peptides), much larger than possible with standard Cartesian coordinate dynamics.For TBSV we considered both the normal form and the high pH form, in which the Ca2+ ions are removed. These calculations lead to a contraction of the protein for both forms (probably because of ignoring the RNA core not observed in the X-ray). © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 21 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200304
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  • 191
    Digitale Medien
    Digitale Medien
    Estimation of changes in side chain configurational entropy in binding and folding: General methods and application to helix formation (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 68-84 
    Details
    ISSN: 0887-3585
    Schlagwort(e): side chain conformation ; protein folding ; protein binding ; helix formation ; helix stability ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Theoretical estimations of changes in side chain configurational entropy are essential for understanding the different contributions to the overall thermodynamic behavior of important biological processes like folding and binding. The configurational entropy of any given side chain in any particular protein can be evaluated from the complete energy profile of the side chain. Calculations of the energy profiles can be performed using the side chain single bond dihedrals as the only independent variables as long as the structures at each value of the dihedrals are allowed to relax through small changes in the valence bond angles. The probabilities of different side chain conformers obtained from these energy profiles are very similar to the conformer populations obtained by analysis of side chain preferences in the proteins of the Protein Data Bank. Also, side chain conformational entropies obtained from the energy profiles agree extremely well with those obtained from the Protein Data Bank conformer populations. Changes in side chain configurational entropy in binding and folding can be computed as differences in conformational entropy because, in most cases, the frequency of the rotational oscillation around the energy minimum of any given conformer does not appear to change significantly in the reaction. Changes of side chain conformational entropy calculated in this way were compared with experimental values. The only available experimental data-the effect of side chain substitution on the stability of α-helices-were used for this comparison. The experimental values were corrected to subtract the solvent contributions. This comparison yields an excellent agreement between calculated and experimental values, validating not only the theoretical estimates but also the separability of the entropic contributions into configurational terms and solvation related terms. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200108
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  • 192
    Digitale Medien
    Digitale Medien
    Microtube batch protein crystallization: Applications to human immunodeficiency virus type 2 (HIV-2) protease and human renin (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 98-102 
    Details
    ISSN: 0887-3585
    Schlagwort(e): X-ray diffraction ; aspartic protease ; AIDS ; recombinant protein ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: For therapeutically relevant targets, the evaluation of enzymes in complex with their inhibitors by cocrystallization and high resolution structural analysis has become a vital component of structure-driven drug design and development. Two approaches, hanging drop vapor diffusion and a novel microtube batch method, were utilized in parallel to grow crystals of recombinant HIV -2 protease and recombinant human renin in complex with inhibitors. In the case of HIV -2 protease in complex with a reduced amide inhibitor, crystallization was achieved only by the microbatch method. In the case of human renin, the addition of precipitant was required for crystal growth. The microbatch method described here is a useful supplementary or alternative approach for screening parameters and generating crystals suitable for high resolution structural analysis. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200110
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  • 193
    Digitale Medien
    Digitale Medien
    Solvent-induced organization: A physical model of folding myoglobin (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 124-138 
    Details
    ISSN: 0887-3585
    Schlagwort(e): leghemoglobin ; hydrophobic ; interactions ; hydrophobicity ; protein folding ; structure prediction ; protein dynamics ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The essential features of the in vitro refolding of myoglobin are expressed in a solvable physical model. Alpha helices are taken as the fundamental collective coordinates of the system, while the refolding is assumed to be mainly driven by solvent-induced hydrophobic forces. A quantitative model of these forces is developed and compared with experimental and theoretical results. The model is then tested by being employed in a simulation scheme designed to mimic solvent effects. Realistic dynamic trajectories of myoglobin are shown as it folds from an extended conformation to a close approximation of the native state. Various suggestive features of the process are discussed. The tenets of the model are further tested by folding the single-chain plant protein leghemoglobin. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200203
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  • 194
    Digitale Medien
    Digitale Medien
    An evaluation of implicit and explicit solvent model systems for the molecular dynamics simulation of bacteriophage T4 lysozyme (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 19-33 
    Details
    ISSN: 0887-3585
    Schlagwort(e): Discover program ; protein dynamics ; computer simulation ; protein motions ; counterions ; dielectric ; protein electrostatics ; aqueous simulation ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: In this report we examine several solvent models for use in molecular dynamics simulations of protein molecules with the Discover program from Biosym Technologies. Our goal was to find a solvent system which strikes a reasonable balance among theoretical rigor, computational efficiency, and experimental reality. We chose phage T4 lysozyme as our model protein and analyzed 14 simulations using different solvent models. We tested both implicit and explicit solvent models using either a linear distance-dependent dielectric or a constant dielectric. Use of a linear distance-dependent dielectric with implicit solvent significantly diminished atomic fluctuations in the protein and kept the protein close to the starting crystal structure. In systems using a constant dielectric and explicit solvent, atomic fluctuations were much greater and the protein was able to sample a larger portion of conformational space. A series of nonbonded cutoff distances (9.0, 11.5, 15.0, 20.0 Å) using both abrupt and smooth truncation of the nonbonded cutoff distances were tested. The method of dual cutoffs was also tested. We found that a minimum nonbonded cutoff distance of 15.0 Å was needed in order to properly couple solvent and solute. Distances shorter than 15.0 Å resulted in a significant temperature gradient between the solvent and solute. In all trajectories using the proprietary Discover switching function, we found significant denaturation in the protein backbone; we were able to run successful trajectories only in those simulations that used no switching function. We were able to significantly reduce the computational burden by using dual cutoffs and still calculate a quality trajectory. In this method, we found that an outer cutoff distance of 15.0 Å and an inner cutoff distance of 11.5 worked well. While a 10 Å shell of explicit water yielded the best results, a 6 A shell of water yielded satisfactory results with nearly a 40% reduction in computational cost. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180105
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  • 195
    Digitale Medien
    Digitale Medien
    Molecular surface representations by sparse critical points (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 94-101 
    Details
    ISSN: 0887-3585
    Schlagwort(e): surface representation ; molecular recognition ; protein docking ; surface triangulation ; molecular graphics ; molecular visualization ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: We have defined a molecular surface representation that describes precisely and concisely the complete molecular surface. The representation consists of a limited number of critical points disposed at key locations over the surface. These points adequately represent the shape and the important characteristics of the surface, despite the fact that they are modest in number. We expect the representation to be useful in areas such as molecular recognition and visualization. In particular, using this representation, we are able to achieve accurate and efficient protein-protein and protein-small molecule docking. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180111
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  • 196
    Digitale Medien
    Digitale Medien
    Lobster enolase crystallized by serendipity (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 390-393 
    Details
    ISSN: 0887-3585
    Schlagwort(e): protein crystallization ; enzyme copurification ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: An unknown protein crystallized from a lobster muscle preparation in which arginine kinase was the majority component. It was identified as enolase by peptide sequencing and activity testing, and a SIRAS electron density map showed its three-dimensional structure to be very similar to that of yeast enolase. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180409
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  • 197
    Digitale Medien
    Digitale Medien
    Crystallographic analysis of oxygenated and deoxygenated states of arthropod hemocyanin shows unusual differences (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 19 (1994), S. 302-309 
    Details
    ISSN: 0887-3585
    Schlagwort(e): dinuclear copper site ; hemocyanin ; oxygen binding ; allosteric regulation ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The X-ray structure of an oxygenated hemocyanin molecule, subunit II of Limulus polyphemus hemocyanin, was determined at 2.4 Å resolution and refined to a crystallographic R-factor of 17.1%. The 73-kDa subunit crystallizes with the symmetry of the space group R32 with one subunit per asymmetric unit forming hexamers with 32 point group symmetry. Molecular oxygen is bound to a dinuclear copper center in the protein's second domain, symmetrically between and equidistant from the two copper atoms. The copper-copper distance in oxygenated Limulus hemocyanin is 3.6 ± 0.2 Å, which is surprisingly 1 Å less than that seen previously in deoxygenated Limulus polyphemus subunit II hemocyanin (Hazes et al., Protein Sci. 2:597, 1993). Away from the oxygen binding sites, the tertiary and quaternary structures of oxygenated and deoxygenated Limulus subunit II hemocyanins are quite similar. A major difference in tertiary structures is seen, however, when the Limulus structures are compared with deoxygenated Panulirus interruptus hemocyanin (Volbeda, A., Hol, W. G. J. J. Mol. Biol. 209:249, 1989) where the position of domain 1 is rotated by 8° with respect to domains 2 and 3. We postulate this rotation plays an important role in cooperativity and regulation of oxygen affinity in all arthropod hemocyanins. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340190405
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  • 198
    Digitale Medien
    Digitale Medien
    Conservation and prediction of solvent accessibility in protein families (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 216-226 
    Details
    ISSN: 0887-3585
    Schlagwort(e): evolutionary information ; multiple alignments ; neural networks ; protein structure prediction ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Currently, the prediction of three-dimensional (3D) protein structure from sequence alone is an exceedingly difficult task. As an intermediate step, a much simpler task has been pursued extensively: predicting 1D strings of secondary structure. Here, we present an analysis of another 1D projection from 3D structure: the relative solvent accessibility of each residue. We show that solvent accessibility is less conserved in 3D homologues than is secondary structure, and hence is predicted less accurately from automatic homology modeling; the correlation coefficient of relative solvent accessibility between 3D homologues is only 0.77, and the average accuracy of predictions based on sequence alignments is only 0.68. The latter number provides an effective upper limit on the accuracy of predicting accessibility from sequence when homology modeling is not possible. We introduce a neural network system that predicts relative solvent accessibility (projected onto ten discrete states) using evolutionary profiles of amino acid substitutions derived from multiple sequence alignments. Evaluated in a cross-validation test on 238 unique proteins, the correlation between predicted and observed relative accessibility is 0.54. Interpreted in terms of a three-state (buried, intermediate, exposed) description of relative accessibility, the fraction of correctly predicted residue states is about 58%. In absolute terms this accuracy appears poor, but given the relatively low conservation of accessibility in 3D families, the network system is not far from its likely optimal performance. The most reliably predicted fraction of the residues (50%) is predicted as accurately as by automatic homology modeling. Prediction is best for buried residues, e.g., 86% of the completely buried sites are correctly predicted as having 0% relative accessibility. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200303
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  • 199
    Digitale Medien
    Digitale Medien
    Molecular dynamics simulations of trp apo-and holorepressors: Domain structure and ligand-protein interaction (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 20 (1994), S. 248-258 
    Details
    ISSN: 0887-3585
    Schlagwort(e): molecular dynamics ; trp-repressor ; ligand ; domain ; dynamic cross-correlation ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Molecular dynamics simulations of the apo- and holo-forms of thetrp-repressor protein were performed under extensively solvated conditions in order to elucidate their dynamic structures and ligand-protein interactions. The root mean square fluctuations calculated from the trajectories agreed with those calculated from X-ray temperature factors. Distance, distance fluctuation, and dynamic cross-correlation maps were drawn to provide information on the dynamic structures and communications among the domains. A three-domain format has been proposed for the crystal structure (Zhang et at., Nature 327:591-597, 1987) namely, helices A-C and F of both subunits make up a central core, and D and E of each subunit forms a DNA binding head. The results of the simulations were mostly consistent with the three-domain format. However, helix F was more flexible and freer than other parts of the central core. The turn DE, the helix-turn-helix DNA binding motif, was free from interactions and correlations with other domains in both forms of the repressor. A comparison of the simulations of the aporepressor and holorepressor showed that tryptophan binding made the DNA-binding helix D more flexible but helix F less flexible. Several amino acid residues in contact with the bound tryptophan were identified as making concerted motions with it. Interaction energies between the corepressor and the amino acid residues of the protein were analyzed; the results were mostly consistent with the mutational experiments. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340200305
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  • 200
    Digitale Medien
    Digitale Medien
    Magnetic resonance studies of the binding of oligonucleotide substrates to mutants of staphylococcal nuclease (1994)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 18 (1994), S. 68-80 
    Details
    ISSN: 0887-3585
    Schlagwort(e): staphylococcal nuclease ; nonproductive substrate binding to ; subsites of ; active site mutants of ; oligonucleotide binding to ; Ca2+ binding to ; Mn2+ binding to ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: By a combination of NMR docking and model building, the substrate binding site on staphylococcal nuclease was found to accommodate a trinucleotide and to consist of three subsites, each interacting with a single nucleotidyl unit of DNA. Binding of the essential Ca2+ activator and substrate cleavage occur between subsites 1 and 2. Hence, catalytically productive binding would span subsites 1 and 2 while nonproductive binding would span subsites 2 and 3. Lys-49 is near subsite 1, and Lys-84 and Tyr-115 interact with substrates at sub site 3 [Weber, D. J., Gittis, A. G., Mullen, G. P., Abeygunawardana, C., Lattman, E. E., Mildvan, A. S. Proteins 13:275-287, 1992]. The proposed locations of these subsites were independently tested by the effects of the K49A, K84A, and Y115A mutations of staphylococcal nuclease on the binding of Mn2+, Ca2+, and the dinucleotide and trinucleotide substrates, 5′-pdTdA, dTdA, and dTdAdG. These three mutants have previously been shown to be fully active and to have CD and 2D NMR spectra very similar to those of the wild-type enzyme (Chuang, W.-J., Weber, D. J., Gittis, A. G., Mildvan, A. S. Proteins 17:36-48, 1993). All three mutant enzymes and their pdTdA and dTdA complexes (but not their dTdAdG complex) bind Mn2+ and Ca2+ more weakly than the wild-type enzyme by factors ranging from 2 to 11. The presence of a terminal phosphate as in 5′-pdTdA raises the affinity of the substrate for staphylococcal nuclease and its three mutants by two orders of magnitude and for the corresponding enzyme-metal complexes by three to four orders of magnitude, suggesting that the terminal phosphate is coordinated by the enzyme-bound divalent cation. Such complexation would result in the nonproductive binding of 5′-pdTdA at subsites 2 and 3. Accordingly, the K84A and Y115A mutations significantly weaken the binding of 5′-pdTdA and its metal to staphylococcal nuclease by factors of 2.2 to 37.8, while the K49A mutation has much smaller or no effect. Such nonproductive binding explains the low activity of staphylococcal nuclease with small substrates, especially those With a terminal phosphate. Similarly, the K84A and Y115A mutations weaken the binding of dTdA and its metal complexes to the enzyme by factors of 3.4 to 13.1 while the K49A mutation has smaller effects indicating significant nonproductive binding of dTdA. The trinucleotide dTdAdG binds more tightly to wild-type and mutant staphylococcal nuclease and to its metal complexes than does the dinucleotide dTdA by factors of 2.4 to 12.2, reflecting the occupancy of an additional subsite. Predominantly productive binding of dTdAdG is indicated by the 1.7- to 8.3-fold lower affinities of the K49A, K84A, and Y115A mutants for the trinucleotide and its metal complexes. The largest effects on dTdAdG binding are seen with the Y115A mutation presumably reflecting the dual role of Tyr-115 both in donating a hydrogen bond to a phosphodiester oxygen between subsites 2 and 3 and in stacking onto the guanine base at subsite 3. © 1994 John Wiley & Sons, Inc.
    Zusätzliches Material: 11 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/prot.340180109
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