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Biomedical subjects

A Philippu

Publications and source records attributed to A Philippu.

At least 91 records · Page 5Linked to original sources

Patterns of histamine release in the brain.

The pattern of histamine release has been investigated in various brain areas of anaesthetized cats and conscious, freely moving rats by the push-pull technique. In the hypothalamus, medial amygdaloid nucleus and mamillary body of the anaesthetized cat, histamine was found to be released according to an ultradian rhythm with a frequency of 1 cycle per 1-2 h. Additionally, oscillations have been observed in the medial amygdaloid nucleus and mamillary body with a frequency of 1 oscillation per 10 min. In the posterior hypothalamus of the conscious rat, histamine is also released rhythmically with a frequency of 1 cycle per 1.5 h. Moreover, the release rate of histamine is increased in the night.

Amygdala↗

The release of endogenous histamine in distinct brain areas is modified by electrical stimulation.

In anaesthetized cats, mamillary bodies, hypothalamic areas and medial amygdaloid nuclei were bilaterally superfused through push-pull cannulae and the effects of the electrical stimulation on the release of endogenous histamine were investigated. Electrical stimulation of the mamillary body increased the release of histamine in the stimulated area, as well as in the contralateral mamillary body. Electrical stimulation of the lateral hypothalamic area enhanced the histamine release in the contralateral hypothalamic area. Stimulation of the posterior hypothalamic area led to a delayed increase in the histamine release in the stimulated area. Stimulation of the medial amygdaloid nucleus reduced the release if histamine in the ipsilateral posterior hypothalamic area, while the histamine release in the contralateral lateral hypothalamic area was enhanced. The results demonstrate that electrical stimulation of distinct brain areas rich in histaminergic neurons may either increase, or decrease the release rate of histamine in the stimulated area and/or in remote brain areas.

Amygdala↗

Carotid occlusion increases the release of endogenous GABA in the nucleus of the solitary tract.

In anaesthetized cats, the nucleus of the solitary tract was bilaterally superfused through push-pull cannulae with artificial cerebrospinal fluid (CSF) and the effect of carotid occlusion on the release of endogenous GABA was investigated. Bilateral carotid occlusion led to a rise in blood pressure which was associated with a very pronounced increase in the release rate of GABA in the nucleus of the solitary tract. The results demonstrate the hypertensive function of GABA in the nucleus of the solitary tract and the importance of GABAergic neurons of this nucleus for the central cardiovascular control.

Animals↗

Pattern of catecholamine release in the nucleus tractus solitarii of the cat.

The release of endogenous dopamine, noradrenaline and adrenaline was studied in the nucleus tractus solitarii (subnucleus medialis) of anaesthetized cats. Two push-pull cannulae were inserted into the right and left nuclei tractus solitarii which were simultaneously superfused with artificial cerebrospinal fluid. The release of the neurotransmitters was determined in the superfusates which were continuously collected in 10 min or 2.5 min time periods for 6 h or 2 h, respectively. Collection of the superfusates in time periods of 10 min showed that the release rates of endogenous dopamine, noradrenaline and adrenaline varied rhythmically according to an ultradian rhythm, the time interval between 2 adjacent phases of high release rate being approximately 1 h. Some of the phases of high release rates of the three endogenous catecholamines timely coincided with each other. Collection of the perfusates in time periods of 2.5 min revealed the existence of additional oscillations with a frequency of about 1 cycle/10 min for dopamine, noradrenaline and adrenaline. The findings suggest that catecholamines are released in the nucleus tractus solitarii according to an ultradian rhythm with low (1 cycle per h) and high (1 cycle per 10 min) frequencies, which might reflect the activity of catecholaminergic neurons in this brain structure.

Animals↗

Release of endogenous catecholamines in the nucleus tractus solitarii during experimentally induced blood pressure changes.

The nucleus tractus solitarii (subnucleus medialis) of anaesthetized cats was bilaterally superfused through push-pull cannulae and the release of endogenous catecholamines (dopamine, noradrenaline and adrenaline) determined in the superfusates. A moderate increase in blood pressure elicited by intravenously injected noradrenaline (0.3 micrograms per kg body weight) reduced the rate of release of endogenous adrenaline, while a pronounced rise in blood pressure (at least 47 mm Hg) evoked by noradrenaline (3 micrograms per kg) or blood injection inhibited the release of adrenaline and noradrenaline in the nucleus tractus solitarii. Bilateral carotid occlusion also diminished the release rates of adrenaline and noradrenaline. Decreases in blood pressure induced by controlled bleeding, intravenous injection of chlorisondamine or nitroprusside did not alter the rates of release of adrenaline or noradrenaline, but the rate of release of endogenous dopamine seemed to be reduced. The decreased adrenaline and noradrenaline release elicited by increases in blood pressure and the reduced release of dopamine induced by decreases in blood pressure may reflect a counteracting mechanism in the nucleus tractus solitarii so as to normalize alterations in blood pressure. The results suggest a hypertensive function of noradrenaline, and possibly a hypotensive role of dopamine at the level of the nucleus tractus solitarii.

Animals↗

Pattern of in vivo release of endogenous histamine in the mamillary body and the amygdala.

The mamillary body and the medial amygdaloid nucleus of cats anaesthetized with sodium pentobarbital were bilaterally and simultaneously superfused through push-pull cannulae with CSF and the release of endogenous histamine was determined in the superfusates. Collection of the superfusates in 10 min time periods revealed that histamine was rhythmically released in the two areas with frequencies of one cycle/90 min (mamillary body) or one cycle/135 min (medial amygdaloid nucleus). Collection of the superfusates in time periods of 2 min revealed the existence of an additional ultradian rhythm with a frequency of approximately one cycle/19 min in both areas. Bilateral lesions of the suprachiasmatic nucleus did not seem to influence the pattern of histamine release in the mamillary body and the medial amygdaloid nucleus, but the rate of histamine release was decreased in the mamillary body. It is concluded that the ultradian rhythms of histamine release in the mamillary body and the medial amygdaloid nucleus are not dependent on the integrity of the suprachiasmatic nucleus. The rate of histamine release in the mamillary body seems to be under the influence of excitatory neurons which originate from the suprachiasmatic nucleus.

Activity Cycles↗

Stereoselectivity of noradrenaline uptake into synaptic vesicles of the rat brain.

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 Km values of the ATP-Mg2+-dependent uptake were found to be different for the two isomers (mumol/l): 3H-(+/-)-noradrenaline 14.9 +/- 2.2 x 10(-1), 3H-(-)-noradrenaline 7.7 +/- 0.5 x 10(-1), 14C-(+)-noradrenaline 17.3 +/- 3.7 x 10(-1), whereas the Vmax 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 x 10(-1) mumol/l) and 3H-(-)-noradrenaline (Ki 17.7 +/- 1.8 x 10(-1) mumol/l), the Ki values being nearly identical with the Km 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.

Adenosine Triphosphate↗

Histamine, histidine decarboxylase and histamine-N-methyltransferase in brain areas of spontaneously hypertensive rats.

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.

Age Factors↗

In vivo release by histamine agonists and antagonists of endogenous catecholamines in the cat hypothalamus.

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 rates 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.

Animals↗

Effects of short-lasting and long-lasting blood pressure changes on the release of endogenous catecholamines in the hypothalamus of the conscious, freely moving rabbit.

In anaesthetized rabbits guide cannulae were stereotaxically inserted into the anterior hypothalamic area and into the posterior hypothalamic nucleus. Additionally, catheters were inserted into the carotid artery and the jugular vein. Some days after the operation push-pull cannulae were inserted through the guide cannulae into the hypothalamic regions of the conscious, freely moving animal. The areas were superfused with artificial CSF and the release of the endogenous catecholamines dopamine, noradrenaline and adrenaline was determined in the superfusates. In the two hypothalamic regions the resting release of the catecholamines rhythmically varied with time at approximately 70 min cycles. A rise in blood pressure induced by the intravenous injection of noradrenaline or tramazoline enhanced the rates of release of the catecholamines in the anterior hypothalamic area. A fall of blood pressure elicited by the intravenous injection of nitroprusside or chlorisondamine decreased the release of the catecholamines in this hypothalamic area. The changes in blood pressure coincided with the changes in the rates of release of the catecholamines in the anterior hypothalamic area. These and previous results concerning changes in the release of endogenous catecholamines in the posterior hypothalamic nucleus also indicate that in the conscious, freely moving rabbit changes in blood pressure lead to counteracting alterations in the release of catecholamines in the two hypothalamic regions.

Animals↗

Release of endogenous histamine in the hypothalamus of anaesthetized cats and conscious, freely moving rabbits.

The hypothalamus of anaesthetized cats and conscious, freely moving rabbits was superfused with CSF through double-walled, push-pull cannulae and the release of endogenous histamine was determined in the superfusates by a radioenzymatic assay. In the posterior hypothalamic area of the anaesthetized cat, the rate of release of endogenous histamine varied rhythmically; phases of high rate of release appeared at 60 min cycles. The release of histamine was increased by electrical stimulation of the superfused area, as well as by hypothalamic superfusion with potassium-rich CSF. In the conscious rabbit, the anterior hypothalamic area and the posterior hypothalamic nucleus were superfused simultaneously. In both regions, the resting release of histamine varied rhythmically at approximately 70 min cycles. Phases of high or low-rate of release in the anterior hypothalamic area coincided with the corresponding phases in the posterior hypothalamic nucleus. The rhythmic release of endogenous histamine in the hypothalamus, as well as the ability of depolarizing stimuli to enhance the release of the amine support the idea that histamine acts as a neurotransmitter in the central nervous system.

Anesthesia↗

Presynaptic regulation of the release of catecholamines in the cat hypothalamus.

The posterior hypothalamus of cats was superfused through a push-pull cannula and the release of endogenous catecholamines was determined in the superfusate. Superfusion with yohimbine, isoprenaline, salbutamol or tazolol increased, while superfusion with propranolol decreased, the release of all three catecholamines. Transection of the brain caudal to the hypothalamus inhibited 'resting' and drug-induced release. It is concluded that alpha- and beta-adrenoceptors of the hypothalamus are involved in the regulation of the release of catecholamines.

Albuterol↗

Hypotension alters the release of catecholamines in the hypothalamus of the conscious rabbit.

The posterior hypothalamic nucleus of conscious, freely moving rabbits was superfused with CSF through a cannula. Intravenous injection of nitroprusside elicited a fall of the arterial blood pressure and increased the rates of release of endogenous catecholamines in the posterior hypothalamic nucleus, while noradrenaline increased the blood pressure but did not change the release of catecholamines. It is concluded that hypotension leads to a counteracting increase in the release of catecholamines in the posterior hypothalamus.

Animals↗

Hypothalamic superfusion with histamine agonists and antagonists modifies the pressor response to hypothalamic stimulation.

The posterior hypothalamus of anaesthetized cats were superfused with CSF through a push-pull cannula and electrically stimulated with its tip. Hypothalamic stimulation elicited a pressor response. Superfusion of the hypothalamus with histamine-containing CSF elicited a concentration-dependent enhancement of the pressor response. The enhancing effect of histamine was abolished, when the hypothalamus was pre-superfused with metiamide, whereas pre-superfusion with mepyramine only slightly inhibited the effect of histamine. Hypothalamic superfusion with dimaprit caused a concentration-dependent increase in the pressor response. The effect of dimaprit was abolished by pre-superfusion of the hypothalamus with metiamide, but it was not affected by pre-superfusion with mepyramine. Superfusion of the hypothalamus with 2-methylhistamine did not affect the pressor response. It is concluded that histamine increases the pressor response to hypothalamic stimulation. The enhancing effect of histamine is mainly due to its action on H2-receptors of the posterior hypothalamus.

Animals↗