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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 103-118 
    ISSN: 1432-1912
    Keywords: Hypothalamus ; Noradrenaline ; Gamma-Aminobutyric Acid ; Electrical Stimulation ; Push-Pull Cannula ; Blood Pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The third ventricle and the aqueduct of anaesthetized cats were cannulated and the posterior area of the hypothalamus was stimulated with a monopolar electrode. Electrical stimulation of the posterior area evoked a rise of the arterial blood pressure which was inhibited by the injection of 0.2 ml of gammaaminobutyric acid (GABA, 2M) into the third ventricle. The impairment of the pressor response to electrical stimulation was accompanied by a fall of the “resting” blood pressure and depression of the respiration, presumably by action of GABA on brain areas in the vicinity of the fourth ventricle. In another series of experiments the posterior area was labelled with (±)-3H-noradrenaline and 2 h later superfused with a push-pull cannula and stimulated with the tip of the cannula. Superfusion with GABA (0.1 or 1 M) evoked a dose-dependent increase of release of catecholamines and enhanced the pressor response to electrical stimulation. 1×10−3 M of GABA enhanced the pressor response without increasing the spontaneous release of catecholamines but potentiated the output of radioactivity during electrical stimulation. Superfusion with sucrose (1 M) did not influence either pressor response or release of radioactive compounds. Superfusion with GABA increased slightly but significantly the relative concentration of catechols in the effluents and reduced that of normetanephrine. Pretreatment of animals with pargyline and tropolone evoked a pronounced increase of the relative concentrations of catechols in the effluent, while those of 3-methoxy-4-hydroxyphenylglycol and 3-methoxy-4-hydroxymandelic acid were strongly reduced. It is concluded that superfusion with high concentrations of GABA enhances the pressor response by increasing the release of catecholamines, while the effect of low GABA concentrations is due to facilitation of release of catecholamines from the adrenergic nerve endings during electrical stimulation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 181-190 
    ISSN: 1432-1912
    Keywords: Caudate Nucleus ; Dopamine ; Ouabain ; Reserpine ; Prenylamine ; Uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Homogenates of the caudate nucleus of the pig were submitted to differential centrifugation. The 20 000 g and 80 000 g fractions were isolated and a part of them was osmotically shocked. The highest dopamine content per mg protein was found in the intact 80 000 g fraction. Incubation experiments with the intact and the osmotically shocked fractions at 25°C revealed that the particles of the intact 20 000 g fraction took up dopamine; the influx of the amine was not enhanced by addition of ATP and magnesium to the incubation medium. On the other hand after osmotic shock the uptake of dopamine into the particles of this fraction was greatly enhanced by addition of ATP and magnesium. The uptake of dopamine into the particles of both intact and osmotically shocked 80 000 g fractions was likewise enhanced by ATP and magnesium. The uptake in all fractions was not influenced by ouabain. The influx of dopamine into the particles of the intact 80 000 g fraction was competitively inhibited by reserpine (K i 0.96×10−8 M) and prenylamine (K i 1.74×10−8 M). It is concluded that the intact 20,000 g fraction contains intact synaptosomes; the uptake of dopamine is independent of the presence of ATP and magnesium. The shocked 20 000 g fraction and the 80 000 g fractions contain synaptic vesicles; the uptake of dopamine into these vesicles is enhanced by ATP and magnesium.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 258 (1967), S. 251-265 
    ISSN: 1432-1912
    Keywords: Stellate ganglion ; Noradrenaline ; Release ; Uptake ; Reserpine ; ATPase ; Ganglion stellatum ; Noradrenalin ; Freisetzung ; Aufnahme ; Reserpin ; ATPase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Noradrenalin speichernde Granula vom Ganglion stellatum des Rindes wurden durch Differentialzentrifugieren isoliert und bei 22°C 45 min lang inkubiert. 2. Die spontane Noradrenalin-Freisetzung aus Ganglien-Granula ist etwa gleich groß wie die aus isolierten Herz- und Nerven-Granula. Sie läßt sich durch Reserpin (0,06 μMol/ml) sowie durch kleine Prenylamin-Konzentrationen (0,03 μMol/ml) hemmen, während große Prenylamin-Konzentrationen (1,2 μMol/ml) eine nahezu vollständige Noradrenalin-Verarmung der Granula verursachen. Bei der Inkubation mit ATP-Magnesium (je 3 μMol/ml) wird wahrscheinlich die Wiederaufnahme des spontan freigesetzten Noradrenalins so stark aktiviert, daß der Noradrenalin-Gehalt der Granula praktisch nicht abnimmt. 3. Isolierte Ganglien-Granula nehmen sowohl durch passive Diffusion als auch durch einen von ATP und Magnesium abhängigen Mechanismus Adrenalin auf. Die durch ATP-Magnesium bedingte Aminaufnahme läßt sich durch Reserpin hemmen. 4. Die über einem Dichtegradienten getrennten Granula stellen eine homogene, mitochondrienfreie Population dar, wie aus elektronenmikroskopischen Untersuchungen sowie aus der Bestimmung der Fumarase-Aktivität der Granula hervorgeht. Sie besitzen eine ATPase-Aktivität, die durch Reserpin und Prenylamin gehemmt wird. 5. Die Ergebnisse sprechen für eine kausale Beziehung zwischen Amin-Transport durch die Membran der sympathischen Ganglien-Granula und ihrer ATPase-Aktivität.
    Notes: Summary 1. The noradrenaline storing granules of stellate ganglia from cattle were isolated by differential centrifugation and incubated for 45 min at 22°C. 2. Noradrenaline is released spontaneously from ganglion granules to about the same extent as from heart and splenic nerve granules. Reserpine (0.06 μmoles/ml) and small concentrations of prenylamine (0.03 μmoles/ml) inhibit the spontaneous release whereas large concentrations of prenylamine (1.2 μmoles/ml) produce an almost complete depletion of noradrenaline. In the presence of ATP-Magnesium (3 μmoles/ml each) the spontaneous noradrenaline release from ganglion granules is inhibited very likely by stimulation of the reuptake mechanism for noradrenaline. 3. Adrenaline is taken up into the isolated ganglion granules by passive diffusion and by an ATP-Magnesium dependent mechanism. Only the latter one is inhibited by reserpine. 4. In order to obtain a preparation free of mitochondria ganglion granules isolated by differential centrifugation were further fractionated over a sucrose density gradient. Electron microscopic studies as well as determinations of the fumarase activity show that the obtained ganglion granules are free of mitochondria and contain practically no fumarase activity. On the other hand they do possess an ATPase activity which is inhibited by reserpine and prenylamine. 5. It is concluded that there exists a causal relationship between the transport of amines through the membrane of the ganglion granules and their ATPase activity.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 258 (1967), S. 238-250 
    ISSN: 1432-1912
    Keywords: Hypothalamus ; Noradrenaline ; Storage ; Calcium ; Acetylcholine ; Hypothalamus ; Noradrenalin ; Speicherung ; Calcium ; Acetylcholin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Schweine-Hypothalami wurden durch Differentialzentrifugieren fraktioniert und der Noradrenalin- sowie der Eiweiß-Stickstoff-Gehalt der gewonnenen sechs Fraktionen bestimmt. Die Fraktionen III (30 000 g), IV (60 000 g) und V (100 000 g) enthalten den größten Noradrenalin-Gehalt pro mg Eiweiß und stellen somit die spezifischen Fraktionen dar, in denen das Noradrenalin hauptsächlich partikulär gebunden vorliegt. Der molare Quotient Noradrenalin/ATP der Fraktion 30 000–100 000 g beträgt 0,56. Die aminspeichernden Vesikel der Fraktion 30 000–100 000 g wurden 60 min lang bei 37°C inkubiert. Die spontane Noradrenalin-Freisetzung ist mit 31% des Ausgangsgehaltes etwa gleich groß wie die spontane Adrenalin-Freisetzung aus isolierten Nebennierenmark-Granula. Reserpin sowie kleine Prenylamin-Konzentrationen (60 nmol/ml) hemmen die spontane Noradrenalin-Freisetzung, während große Prenylamin-Konzentrationen (1,2 μmol/ml) eine fast vollständige Noradrenalin-Verarmung der Vesikel verursachen. Inkubation mit verschiedenen Calcium-Konzentrationen verursacht eine dosisabhängige Noradrenalin-Freisetzung. Acetylcholin ist ebenfalls in der Lage, die spontane Noradrenalin-Freisetzung zu erhöhen. Bei der gleichzeitigen Inkubation mit Calcium und Acetylcholin konnte keine Addition der Wirkungen der beiden Substanzen festgestellt werden. Reserpin vermag die durch Calcium bedingte Noradrenalin-Freisetzung zu hemmen.
    Notes: Summary In order to study the subcellular distribution of noradrenaline in the hypothalamus this region was removed from pig brains and fractionated by differential centrifugation. From the six obtained fractions fraction III (30,000 g), IV, (60,000 g), and V (100,000 g) contain the highest amounts of noradrenaline per mg protein (69, 60 and 47 ng/mg protein respectively). These fractions represent therefore the main noradrenaline storing fractions of the hypothalamus. The molar ratio noradrenaline/ATP of the vesicles of the fraction 30,000–100,000 g is 0.56. The noradrenaline storing vesicles of the fraction 30,000–100,000 g of the hypothalamus were incubated for 60 min at 37°C. The spontaneous release of noradrenaline amounts to 31% of the original noradrenaline content of the vesicles. It is therefore of the same order of magnitude as the spontaneous release of adrenaline from isolated granules of the suprarenal medulla. Reserpine and prenylamine (60 nmoles/ml) inhibit the spontaneous release of noradrenaline whereas 1.2 μmoles prenylamine/ml deplete the vesicles almost completely. Incubation of the hypothalamus vesicles with calcium chloride (0.31–5.0 μmoles/ml) causes a dose dependent release of noradrenaline. Acetylcholine (55 nmoles/ml) is also able to increase the spontaneous release of noradrenaline. By simultaneous incubation with calcium and acetylcholine no addition of the effects of both substances on the release of noradrenaline could be observed. Reserpine prevents the calcium-induced release of noradrenaline.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 271 (1971), S. 311-319 
    ISSN: 1432-1912
    Keywords: Hypothalamus ; Noradrenaline ; Electrical Stimulation ; Chemical Sympathectomy ; Blood Pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The third ventricle and the aqueduct of the anaesthetized cat were cannulated and the hypothalamus was superfused with artificial cerebrospinal fluid. Electrical stimulation of the nucleus posterior of the hypothalamus elicited a rise of the blood pressure of 58±3 mm Hg (n=20). Superfusion of the hypothalamus with artificial cerebrospinal fluid containing bretylium (5×10−3 M) caused a gradual and long lasting impairment of the rise of blood pressure due to stimulation of the nucleus posterior. Tetracaine (1×10−3 M) diminished the rise of blood pressure to about the same extent as did 5×10−3M of bretylium; the inhibitory action of tetracaine was completely reversed within 120 min. Pretreatment of cats with 6-hydroxydopamine, which was applied through a Collison cannula implanted into the lateral ventricle, evoked a decrease of the noradrenaline content of the hypothalamus and of the rest of the brain and an impairment of the rise of blood pressure during stimulation of the nucleus posterior (33±3 mm Hg;n=6). The blood pressure of the anaesthetized cats was not affected by pretreatment with 6-hydroxydopamine. Superfusion of the hypothalamus with desipramine (1×10−4M) enhanced the rise of blood pressure elicited by electrical stimulation. The results are compatible with the assumption that the rise of blood pressure during stimulation of the nucleus posterior of the hypothalamus is mediated by adrenergic neurons of the brain.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 621-625 
    ISSN: 1432-1912
    Keywords: Synaptic vesicles ; Uptake ; Stereoselectivity ; Noradrenaline ; Rat brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the stereoselectivity of the ATP-Mg2+-dependent uptake of noradrenaline, synaptic vesicles were isolated from the rat brain by differential centrifugation and incubated with 3H-(±)-, 3H-(−)- or 14C-(+)-noradrenaline in the absence and in the presence of ATP-Mg2+. The K m values of the ATP-Mg2+-dependent uptake were found to be different for the two isomers (μmol/l): 3H(±)-noradrenaline 14.9 ± 2.2 × 10−1, 3H-(−)-noradrenaline 7.7 ± 0.5 × 10−1, 14C-(+)-noradrenaline 17.3 ± 3.7 × 10−1, whereas the V maX of the racemate was identical with those of the two isomers (pmol/mg protein/min): 3H-(±)-noradrenaline 5.5 ± 0.4, 3H-(−)-noradrenaline 4.9 + 0.1, 14C-(+)-noradrenaline 5.1 ± 0.4. Moreover, (+)-noradrenaline inhibited competitively the ATP-Mg2+-dependent uptake of 3H-(±)-noradrenaline (Ki 19.2 + 1.0 × 10−1 μmol/l) and 3H-(−)-noradrenaline (Ki 17.7 ± 1.8 × 10−1 μmol/l), the Ki values being nearly identical with the K m of the ATP-Mg2+-dependent uptake of 14C-(+)-noradrenaline. It is concluded that the ATP-Mg2+-dependent uptake of noradrenaline into synaptic vesicles of the rat brain is stereoselective and that both isomers share the same transport system.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 344 (1991), S. 183-186 
    ISSN: 1432-1912
    Keywords: Push-pull cannula ; Histamine ; Noradrenaline ; Clonidine ; Yohimbine ; Idazoxan ; Conscious rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The modulation of the histamine release from histaminergic neurons by noradrenergic neurons was investigated by the push-pull technique. The posterior hypothalamus of the conscious, freely moving rat was superfused with artificial CSF through a push-pull cannula and the release of endogenous histamine was determined in the superfusate. Hypothalamic superfusion with a potassium-rich CSF enhanced the release rate of histamine. Superfusion with the α2-agonists noradrenaline or clonidine diminished the release rate of histamine. Moreover, clonidine abolished the potassium-induced increase in the histamine release. Superfusion with the α2-antagonists yohimbine or idazoxan enhanced the release rate of histamine. It is concluded that noradrenaline released from noradrenergic neurons of the hypothalamus modulates the release of histamine from histaminergic neurons by stimulating α2-adrenoreceptors located on histaminergic nerve terminals.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 347 (1993), S. 28-33 
    ISSN: 1432-1912
    Keywords: Ultradian rhythm ; Hypothalamus ; Pushpull cannula ; Dopamine ; Noradrenaline ; Adrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the patterns of catecholamine release in the brain, the hypothalamus of conscious, freely moving rats was superfused through a push-pull cannula with artificial cerebrospinal fluid and the catecholamines dopamine, noradrenaline and adrenaline were determined in the superfusate radioenzymatically. Superfusate was continuously collected in time periods of 20 min for at least 20h. Dopamine, noradrenaline and adrenaline release rates fluctuated according to an ultradian rhythm with a frequency of 1 cycle/92 min (dopamine and noradrenaline) or 99 min (adrenaline). Additionally, the three catecholamines were released according to an ultradian rhythm with the following frequencies: noradrenaline and adrenaline 1 cycle/ 12 h, dopamine 1 cycle/8 h. The release rates of dopamine and adrenaline were similar during light and dark periods, while the release rate of noradrenaline in the dark period was slightly lower than that during the light period. It is concluded that in the hypothalamus of the conscious rat the release rates of dopamine, noradrenaline and adrenaline fluctuate according to two ultradian rhythms with different frequencies.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 339-345 
    ISSN: 1432-1912
    Keywords: Locus coeruleus ; Dopamine ; Noradrenaline ; Adrenaline ; Veratridine ; Tetrodotoxin ; Push-pull cannula ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the release of endogenous dopamine, noradrenaline and adrenaline in the locus coeruleus, this brain area was superfused with artificial cerebrospinal fluid (CSF) through push-pull cannulae and the release of catecholamines was determined in the superfusate radioenzymatically. Collection of superfusates in time periods of 10 min revealed that release rates of the three catecholamines fluctuated, thus pointing to the existence of ultradian rhythms with following mean periods (minutes per cycle): noradrenaline 52±4, dopamine 37±2, adrenaline 36±2. The rhythm frequency of noradrenaline was significantly lower than the frequencies of dopamine and adrenaline. When the locus coeruleus was superfused with neuroactive drugs, superfusates were collected in time periods of 3 min. Superfusion with tetrodotoxin (1 μmol 1−1) for 12 min elicited a prompt and sustained decrease (−70%) in the release rates of dopamine and adrenaline. The release rate of noradrenaline was also reduced, although to a lesser extent (−40%). Superfusion with veratridine (50 μmol 1−1) led to an immediate and very pronounced enhancement in the release rates of dopamine, noradrenaline and adrenaline. The veratridine-induced increase in catecholamine outflow was decreased strongly by simultaneous superfusion with tetrodotoxin. The findings suggest that the release of endogenous catecholamines in the locus coeruleus fluctuates according to ultradian rhythms. Changes in the release on superfusion with veratridine and tetrodotoxin demonstrate the neuronal origin of the three catecholamines. The observed differences in the release characteristics between noradrenaline on the one hand and dopamine and adrenaline on the other might indicate that noradrenaline is partly released from somatodendritic sites of the noradrenergic cell bodies in the locus coeruleus.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 460-465 
    ISSN: 1432-1912
    Keywords: Key words Spontaneously hypertensive rats ; Serotonin ; release ; Locus coeruleus ; Noradrenaline ; Sodium ; nitroprusside ; Noise ; Tail pinch ; Push-pull superfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present work was to clarify whether differences exist between the release of endogenous serotonin in the locus coeruleus of normotensive and hypertensive rats. The locus coeruleus was superfused with artificial cerebrospinal fluid (aCSF) through a push-pull cannula and serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in the superfusate by HPLC combined with electrochemical detection. Compared with normotensive Wistar-Kyoto (WKY) rats, the basal release rate of serotonin in the locus coeruleus of spontaneously hypertensive rats (SHR) was increased more than twofold. Intravenous infusion of noradrenaline (4 μg/kg min) increased mean arterial blood pressure to the same extent in hypertensive and normotensive rats. The pressor response was associated with an increased serotonin release. In WKY rats, the release of serotonin in the locus coeruleus evoked by noradrenaline infusion was more pronounced than in SHR. In WKY rats, intravenous infusion of sodium nitroprusside (150 μg/kg min) led to a fall in blood pressure which was less pronounced and lasted shorter than in SHR. The depressor response was associated with decreased serotonin release. In WKY rats, the decrease in serotonin release evoked by sodium nitroprusside was more pronounced and lasted longer than in SHR. Neither noradrenaline nor sodium nitroprusside influenced the outflow of 5-HIAA. The sensory stimuli noise and tail pinch led to a slight rise in arterial blood pressure which was similar in WKY rats and SHR. These stimuli enhanced the release rate of serotonin and the outflow of 5-HIAA to the same extent in the locus coeruleus of normotensive and hypertensive rats. The findings suggest that the enhanced release of serotonin in the locus coeruleus of genetically hypertensive rats reflects a mechanism counteracting the disturbed blood pressure homeostasis. Stressors influence blood pressure and release of serotonin in the locus coeruleus of SHR and WKY rats to the same extent.
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