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  • 1
    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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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 326 (1984), S. 116-123 
    ISSN: 1432-1912
    Keywords: Hypothalamus ; Push-pull cannula ; Catecholamines ; Histamine ; Histamine receptor agonists ; Histamine receptor antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The posterior hypothalamus of anaesthetized cats was superfused through a push-pull cannula with histamine agonists and antagonists and the release of endogenous catecholamines was determined in the superfusate. Hypothalamic superfusion with histamine, 2-methylhistamine (H1-agonist), dimaprit (H2-agonist) or metiamide (H2-antagonist) enhanced the release of the catecholamines dopamine, noradrenaline and adrenaline. The releasing effects of these substances depended on the presence of calcium ions. Superfusion with 2-pyridylethylamine (H1-agonist) was virtually ineffective, while superfusion with 2-thiazolethylamine (H1-agonist) enhanced the rate of release of noradrenaline and adrenaline without influencing the release of dopamine. Superfusion with mepyramine (H1-antagonist) inhibited the release of noradrenaline and adrenaline without affecting the release of dopamine. Hypothalamic superfusion with a concentration of procaine which was equi-anaesthetic to that of mepyramine was ineffective. Ranitidine (H2-antagonist) did not alter the rates of release of the catecholamines. The releasing effect of histamine was inhibited on hypothalamic superfusion with mepyramine and ranitidine. Ranitidine also inhibited the releasing effects of dimaprit and 2-methylhistamine thus indicating that the releasing action of the latter compound was mainly due to stimulation of H2-receptors. These data suggest that blockade of H1-receptors of the posterior hypothalamus reduces the release of noradrenaline and adrenaline, while stimulation of H1-receptors seems to increase the rates of release of these two catecholamines. Stimulation of H2-receptors enhances the release of all three catecholamines. Thus, dopaminergic neurones of the hypothalamus seem to possess H2-receptors, while noradrenergic and adrenergic neurones possess H1- and H2-receptors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 343 (1991), S. 307-310 
    ISSN: 1432-1912
    Keywords: Histamine ; Brain ; Histidine decarboxylase ; Blood pressure ; α-Fluoromethylhistidine ; Spontaneously hypertensive rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histaminergic neurons of the brain have been implicated in genetic hypertension. We investigated the effect of inhibition of histamine synthesis by α-fluoromethylhistidine (α-FMH), the irreversible inhibitor of histidine decarboxylase, on the development and maintenance of hypertension in spontaneously hypertensive rats. Young (3-week-old) and adult (7-week-old) rats were treated with α-fluoromethylhistidine for 29 and 13 days, respectively. Treatment of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats with α-fluoromethylhistidine led to a pronounced decrease in the histidine decarboxylase activity and in the histamine concentration in the brain (hypothalamus, brainstem, cortex —midbrain). In adult spontaneously hypertensive rats, the development of hypertension was not influenced by α-fluoromethylhistidine. In young spontaneously hypertensive rats, α-fluoromethylhistidine led to a transient delay in the development of hypertension which was followed by a transient tendency to increased blood pressure. It is concluded that histaminergic neurons of the brain play only a subordinate role, if any at all, in the development of hypertension in spontaneously hypertensive rats.
    Type of Medium: Electronic Resource
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  • 4
    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.
    Type of Medium: Electronic Resource
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  • 5
    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.
    Type of Medium: Electronic Resource
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  • 6
    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.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 573-576 
    ISSN: 1432-1912
    Keywords: Histamine ; Histidine decarboxylase ; Histamine-N-methyltransferase ; Brain areas ; SHR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histamine levels, histidine decarboxylase and histamine-N-methyltransferase activities were determined in various brain areas of young (9-week old) and adult (18-week old) normotensive rats (WKY) and hypertensive rats (SHR). When compared with WKY, histamine levels were increased in the anterior and posterior hypothalamus of young and adult SHR, as well as in the brainstem of young SHR. Histidine decarboxylase activity was unchanged in the posterior hypothalamus and in the medulla oblongata of young and adult SHR as well as in the anterior hypothalamus of young SHR, but it was slightly decreased in the anterior hypothalamus of adult SHR. Histidine decarboxylase activity was enhanced in the cortex-midbrain of young, as well as adult SHR, histamine-N-methyltransferase in the cortex-midbrain of young SHR. The following differences were found between young and adult rats: histamine levels were elevated in the cortex-midbrain of adult WKY and SHR. In the cortex-midbrain and brainstem of adult WKY and SHR histidine decarboxylase activity was also increased, while histamine-N-methyltransferase activity was elevated in the cortex-midbrain of adult WKY. The findings show changes in histamine levels, histidine decarboxylase and histamine-N-methyltransferase activities in SHR and suggest involvement of histaminergic neurons in hypertension. The activity of histaminergic neurons of adult rats seems to be higher than that of young animals.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 282 (1974), S. 1-8 
    ISSN: 1432-1912
    Keywords: Hypothalamus ; Release ; Noradrenaline ; Dopamine ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The posterior hypothalamus of cats immobilized with gallamine was superfused through a push-pull cannula with artificial cerebrospinal fluid. Addition of3H-tyrosine into the superfusing fluid led to synthesis of3H-catecholamines which were released spontaneously. Separation of the3H-catecholamines by column chromatography or their acetylation and separation by paper chromatography revealed that both3H-noradrenaline and3H-dopamine were released. In most experiments3H-noradrenaline represented about 10 to 25% of total3H-catecholamines. Superfusion of the hypothalamus with amphetamine (1×10−5 M) enhanced the release of total3H-catecholamines, the release of3H-noradrenaline being relatively more enhanced than that of3H-dopamine. Determination of the readioactive compounds in the hypothalamus at the end of the experiments showed that total3H-catecholamines represented 3% of3H-tyrosine. About 15% of the total3H-catecholamines were due to3H-noradrenaline and 85% to3H-dopamine.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 191-204 
    ISSN: 1432-1912
    Keywords: Synaptic Vesicles ; Dopamine ; GABA ; Serotonin ; Histamine ; ATP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dopamine-containing vesicles were isolated from the caudate nucleus of the pig by differential centrifugation and incubated with 14C-serotonin (14C-5-HT), 14C-gamma-aminobutyric acid (14C-GABA), 14C-dopamine or 14C-histamine. At 25°C the uptake of 14C-5-HT and 14C-GABA was enhanced by ATP and magnesium. The Km for the uptake of 14C-5-HT in the presence of ATP and magnesium was 0.67×10−6 M, that of 14C-GABA 1.33×10−4 M. 14C-Histamine was also taken up into the vesicles but its uptake was not influenced by ATP and magnesim. The ATP-magnesium-dependent uptake of 14C-5-HT and 14C-GABA was abolished at 0°C. At 37°C the accumulation of 14C-GABA in the presence of ATP and magnesium reached a steady state after 20 min, while the accumulation of 14C-5-HT reached a maximum after 2.5 min of incubation and then gradually declined. Osmotic lysis of the vesicles followed by sonication abolished the enhanced uptake of 14C-GABA, 14C-5-HT and 14C-dopamine in the presence of ATP and magnesium. Determination of the endogenous contents of the vesicles revealed 14.6 pmoles per mg protein for 5-HT and 22.7 nmoles per mg protein for GABA. It is concluded that the caudate nucles preparation used in this study contains not only dopamine-storing vesicles able to take up biogenic amines but also GABA-containing vesicles which take up GABA by an ATP-magnesium-dependent process.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 300 (1977), S. 25-30 
    ISSN: 1432-1912
    Keywords: Synaptic vesicles ; Uptake ; Dopamine ; Tyramine ; Reserpine ; Filtration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synaptic vesicles isolated from the caudate nucleus of the pig were preincubated with reserpine, serotonin or tyramine at concentrations which caused a 90% inhibition of the ATP-Mg2+-dependent uptake of 14C-dopamine. The preincubated vesicles were sedimented by centrifugation and resuspended in drug-free buffer. The vesicles were incubated with 14C-dopamine in the presence or in the absence of ATP-Mg2+; at the end of the incubation period they were separated from the incubation medium by centrifugation. The inhibitory effect of reserpine on the ATP-Mg2+-dependent uptake of 14C-dopamine was slightly diminished, that of serotonin reduced while the inhibitory effect of tyramine was abolished. Hence, tyramine seems to be more easily removable than the other substances. In another series of experiments the vesicles were incubated with 3H-tyramine and immediately separated by filtration through membrane filters. Addition of ATP-Mg2+ enhanced the uptake of 3H-tyramine. The Km of the ATP-Mg2+-dependent uptake of 3H-tyramine was 1.4×10−7 M, the Vmax 29.2 pmoles/mg protein/min. At 0°C the uptake of 3H-tyramine in the absence of ATP-Mg2+ was reduced, that in the presence of ATP-Mg2+ abolished. Incubation of the vesicles with 3H-dopamine revealed K m and V max values similar to those previously found when the vesicles were isolated from the incubation medium by centrifugation. Incubation in the presence of reserpine inhibited the ATP-Mg2+-dependent uptake of 3H-tyramine (IC50 1.4×10−8 M) and 3H-dopamine (IC50 4.1×10−8 M). The results demonstrate that tyramine is taken up into the vesicles by a process which is dependent on ATP-Mg2+ and temperature. Failure of previous attempts to prove an ATP-Mg2+-dependent uptake of tyramine when the vesicles were separated by centrifugation seems to be due to release of the accumulated tyramine during the centrifugation procedure.
    Type of Medium: Electronic Resource
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