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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract We have developed and used a novel technique to investigate the effects of lithium and other psychotropic drugs on the cation-transporting properties of the sodium- and potassium-activated ATPase enzyme (Na+, K+-ATPase) in intact synaptosomes. Rubidium-86 uptake into intact synaptosomes is an active process and is inhibited by ∼75% in the presence of the Na+, K+-ATPase inhibitor acetylstrophanthidin. In vitro addition of lithium to synaptosomes prepared from untreated mice causes a progressive inhibition of acetylstrophanthidin-sensitive 86Rb uptake, but only at concentrations higher than the clinical therapeutic range. However, pretreatment of mice for 14 days in vivo with lithium, carbamazepine, and haloperidol, but not phenytoin, causes a significant stimulation of 86Rb uptake into synaptosomes via Na+, K+-ATPase.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 18 (1971), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— The effect of l-tryptophan loading upon the amount of 5-HT accumulating in the brains of rats pretreated with a monoamine oxidase inhibitor was studied. The amount of brain 5-HT accumulated increased with increasing tryptophan dosages and brain tryptophan concentrations up to a tryptophan dose of 120 mg/kg body wt. and a brain tryptophan of about 70 μg/g brain. Above this dose and concentration no further increase in brain 5-HT accumulation occurred. After monoamine oxidase inhibition and tryptophan loading gross hyperactivity and hyperpyrexia occurred. Monoamine oxidase inhibition, tryptophan administration and intact aromatic amino acid decarboxylase activity were all collectively essential for the production of hyperactivity and hyperpyrexia. DL-Parachlorophenyl-alanine prevented both the occurrence of hyperactivity and the increased accumulation of, brain 5-HT. Indices of hyperactivity correlated with the amount of brain 5-HT accumulating in 1 h after tryptophan loading but not with the overall concentration of brain 5-HT, suggesting that hyperactivity was dependent upon the rate of 5-HT synthesis. Reserpine and tetra-benazine pretreatment speeded the onset and rate of development of the hyperactive state without altering the synthesis of brain 5-HT. It is suggested that when monoamine oxidase is inhibited and the rate of 5-HT synthesis is increased, granular uptake and storage of 5-HT and other rate-limiting mechanisms for 5-HT inactivation are unable to prevent 5-HT 'spilling over’to produce hyperactivity.The crucial dependence of 5-HT synthesis upon brain tryptophan concentration and the ability of intraneuronal metabolism, when monoamine oxidase activity is intact, to cope with increased 5-HT synthesis and prevent ‘spillover’, raise the possibility that brain 5-HT synthesis is normally in excess of functional needs, and suggest that intraneuronal metabolism and the intraneuronal organization of 5-HT pools are of more importance than synthesis in regulating the amount of 5-HT available for functional activity.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 17 (1970), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Crude mitochondrial fractions prepared from rat brains took up l-tryptophan. The component of the crude mitochondrial fraction responsible for this uptake is the synaptosome. After uptake of tryptophan occurred, rupture of synaptosomes released 97 per cent of the tryptophan unchanged. Rupture of synaptosomes abolished uptake.Penetration of the limiting membrane of synaptosomes by l-tryptophan both as influx and efflux was studied. Uptake of l-tryptophan was rapid, temperature dependent, partially inhibited by cyanide, 2-deoxy-d-glucose and ouabain, but apparently unaffected by low external sodium ion concentrations. d-tryptophan was a poor inhibiteur of l-tryptophan uptake. Concentration gradients Internal: external of up to 4:1 were achieved. Kinetic studies on l-tryptophan uptake and its competitive inhibition by l-phenylalanine indicated a saturable carrier-mediated transport system, present in the rat at birth. l-Tryptophan efflux from preloaded synaptosomes was markedly stimulated by certain arrino acids and its influx stimulated by preloading with l-tryptophan. This countertransport is further evidence for carrier-mediated or facilitated diffusion. On the basis of countertransport data there seem to be at least two systems for transporting amino acids across synaptosomal membrane.The relevance of these studies to the role of l-tryptophan as the initial precursor of brain 5-hydroxytryptamine is examined.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Corticosterone ; Muscarinic agonists ; Serotoninergic agonists ; α-Adrenoceptor agonists ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A method is described for demonstrating the hypothalamic control of corticosterone in the intact rat. Oxotremorine 0.01–0.05 mg/kg IP and 5-hydroxy-l-tryptophan 1–50 mg/kg IP raise plasma corticosterone levels in dose-related fashion. The oxotremorine response is blocked by atropine 1 mg/kg SC and the 5-hydroxy-l-tryptophan response by mianserin 10 mg/kg IP. α-Methylparatyrosine methyl ester 400 mg/kg IP raises plasma corticosterone levels 14–16 h later. This rise can be suppressed by clonidine 0.01–0.05 mg/kg IP and this suppression is antogonized by piperoxane 5–50 mg/kg IP. Apomorphine 5 mg/kg IP does not lower plasma corticosterone levels in rats pre-treated with α-methylparatyrosine. The response to oxotremorine cannot be blocked by atropine methylbromide or by mianserin. The response to 5-hydroxy-l-tryptophan is unaffected by benserazide or atropine sulphate. These data suggest separate cholinergic and serotoninergic facilitation of corticosterone release in the intact rat. The stimulating drugs used appear to be acting centrally. The data also support the presence of a noradrenergic inhibitory system mediated by α-adrenoceptors. Dopaminergic receptors appear to play no part in the central control of corticosterone secretion after pre-treatment with α-methylparatyrosine.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Neuroleptics ; Cyclic AMP ; Caudate nucleus ; Dopamine ; Hyperactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Injection of rats with tranylcypromine and l-dopa increased brain dopamine concentrations and produced a behavioural syndrome that includes hyper-activity. It also elevated caudate nucleus cyclic AMP concentrations by approximately 50% in vivo, probably by stimulating dopamine receptors. Pretreatment with chlorpromazine inhibited both the tranyl-cypromine/l-dopa-induced behaviour and elevated cyclic AMP concentrations in a dose-dependent manner. Haloperidol and α-flupenthixol also inhibited both effects, while β-flupenthixol and pimozide were without effect. Since none of these drugs altered the tranylcypromine/l-dopa-induced rise of brain dopamine, it is likely that they produced their effect by inhibiting dopamine-sensitive adenylate cyclase. A good correlation was found to exist between the neuroleptic inhibition of both the increased behavioural activity and the increased caudate nucleus cyclic AMP concentrations produced by tranylcypromine and l-dopa.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Electroconvulsive shock ; Electronvulsive therapy ; 5-Hydroxytryptamine ; Behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treatment of rats with one electroconvulsive shock (ECS) per day for 10 days enhanced the hyperactivity syndrome produced by administration of tranylcypromine (10 mg kg-1) and l-tryptophan (50 mg kg-1) given 24 h after the final shock. Similar enhancement was seen whether the shock was alternating sinusoidal or direct current (fractionated), whether it was given through unilaterally or bilaterally placed electrodes and whether or not a neuromuscular blocking agent (fazadinium) was used. Five shocks spread over 10 days or 8 shocks spread over 17 days were similarly effective, whilst 8 shocks in 1 day were ineffective. Therefore when ECS are given to rats in ways similar to those in which electroconvulsive therapy is given to patients with depression, enhancement of behavioural responses to increased 5-HT function is produced.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Lithium ; Tryptophan ; Prolactin ; Growth hormone ; 5-HT receptors ; Imipramine binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of lithium on serotonin (5-HT)-mediated responses in the brain was assessed by measuring changes in the prolactin (PRL) and growth hormone (GH) responses to l-tryptophan (LTP) in eight normal subjects. On the 4th day of lithium treatment the PRL responses were significantly enhanced, and this enhancement was still apparent after 20 days' treatment. In contrast, GH responses to LTP were not altered. Lithium had no effect on platelet 5-HT content, platelet imipramine binding and platelet 5-HT receptor binding. The ability of lithium to enhance some aspects of brain 5-HT function may be important in its mode of action in manic-depressive illness and may be particularly relevant to its potentiation of the antidepressant effect of tricyclic antidepressants.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1440
    Keywords: Cardiac glycosides ; Cation transport ; Herzglykoside ; Kationentransport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Effekte von Digoxin auf die Mechanismen des Kationentransportes wurden an den Erythrozyten der Patienten untersucht. Die Studien wurden während Digoxinbehandlung bei Vorhofflimmern und bei Herzinsuffizienz mit Sinusrhythmus durchgeführt. Die Resultate zeigen, daß während kurzzeitiger Behandlung mit Digoxin die Rezeptoren für Herzglykoside an den Erythrozyten besetzt werden, woraus eine Hemmung des aktiven Kationentransportes resultiert. Diese Wirkungen zeigen eine gute Korrelation mit dem klinischen Erfolg der Behandlung. Während Langzeitbehandlung lassen sich diese Wirkungen jedoch nicht nachweisen. Dieser Befund legt nahe, daß dabei eine pharmakologische Toleranz gegenüber den Digoxinwirkungen eintritt. Die klinische Bedeutung dieser Befunde wird diskutiert.
    Notes: Summary We have measured the effects of digoxin on the cation transport mechanisms of patients' erythrocytes during treatment with digoxin for atrial fibrillation and cardiac failure in sinus rhythm. The results show that during short-term treatment with digoxin there is occupation of erythrocytic cardiac glycoside receptors by digoxin with resultant inhibition of active cation transport. These effects correlate well with the patients' clinical responses to treatment. During long-term treatment, however, these effects are not seen, suggesting that there is pharmacological tolerance to the effects of digoxin. The clinical implications of these results are discussed.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 253 (1975), S. 58-60 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] RNA polymerase catalyses nucleophilic attack by an alcohol group on the a-phosphorus of ribonucleoside triphosphates. Adenyl cyclase also belongs to this functional group of enzymes and in the studies reported here the exotoxin has been shown to be a competitive inhibitor of adenyl cyclase, to ...
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  • 10
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1. Intensity of the withdrawal syndrome in mice injected with 10 //g/kg naloxone. The ordinate represents the mean numher of jumps in an 8 min period beginning 3 min after the injection of naloxone. No significant difference was seen between groups injected with morphine alone (o-o) or both ...
    Type of Medium: Electronic Resource
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