Biomedical subjects

A Philippu

Publications and source records attributed to A Philippu.

At least 73 records · Page 4Linked to original sources

PubMed1994

Release of acetylcholine in the ventral striatum is influenced by histamine receptors.

To investigate whether histamine receptor ligands influence the in vivo-release of acetylcholine in the ventral striatum, this brain region was superfused with histamine receptor agonists or antagonists through a push-pull cannula and drug effects on the release of acetylcholine were investigated. Histamine, the H1 receptor agonist 2-thiazolyl-ethylamine and the H3 receptor antagonist thioperamide enhanced acetylcholine release, while the H3 receptor agonist (R)-alpha-methylhistamine was ineffective. The results indicate that H1 receptors and H3 receptors modulate acetylcholine release. The thioperamide-induced increase of acetylcholine release might be exerted via H3-receptors located on cholinergic terminals. Alternatively, thioperamide might enhance acetylcholine release by increasing endogenous histamine release via H3 autoreceptors. It is concluded that, via stimulation of striatal H1- and H3 receptors, histaminergic neurons are involved in the regulation of cholinergic neuronal activity in the ventral striatum.

Acetylcholine↗

PubMed1994

[Effects of arterial blood pressure change on release of GABA in the posterior hypothalamus conscious of freely moving rats].

Push-pull superfusion technique was used to investigate the release of endogenous gamma-aminobutyric acid (GABA) in the posterior hypothalamus of the conscious, freely moving rat in response to peripherally applied drugs or experimentally induced blood pressure changes. The rise in blood pressure elicited by intravenous infusion of phenylephrine (15 micrograms.kg-1.min-1) or blood (3 ml/100 g) was associated with an increased rate of GABA release in the posterior hypothalamus. Hypotension produced by nitroprusside (30 micrograms.kg-1.min-1), chlorisondamine (3 mg.kg-1,iv) and controlled bleeding (3 ml/100 g) led to a counteracting decrease in hypothalamic GABA outflow. This finding suggests that GABAergic neurons of the conscious, freely moving rat in the posterior hypothalamus are involved in cardiovascular control and possess a hypotensive function.

Animals↗

PubMed1993

Taurine release in the hypothalamus is altered by blood pressure changes and neuroactive drugs.

The release of endogenous taurine was determined in the posterior hypothalamus of the conscious, freely moving rat by using the push-pull superfusion technique. At the start of superfusion, the outflow of endogenous taurine declined rapidly with a half-time of 7.9 min and reached a steady state after approximately 1 h. Thereafter, the release rate was constant and amounted to 2.6 +/- 0.3 pmol/min. During depolarization either with K+ (50 or 90 mM) or veratridine (1 or 10 microM), taurine outflow was increased in a concentration-dependent way. Hypothalamic superfusion with tetrodotoxin (1 microM) elicited a sustained decrease in the taurine release to 60% of the control values. Intravenous infusion of noradrenaline led to a rise in blood pressure (45 mm Hg) and enhanced the release of taurine in the hypothalamus. A fall of blood pressure (30 mm Hg) caused by an intravenous infusion of nitroprusside diminished taurine outflow. The results suggest that a considerable amount of the taurine detected is released from hypothalamic neurons. Changes in the release rate of taurine by experimentally induced alterations of blood pressure indicate that, in the posterior hypothalamus, the amino acid might play an important role as a neurotransmitter or neuromodulator possessing a hypotensive function.

Animals↗

PubMed1993

Induction of GTP cyclohydrolase I by bacterial lipopolysaccharide in the rat.

A 2- to 3-fold increase of GTP cyclohydrolase I (E.C. 3.5.4.16), the key enzyme of tetrahydrobiopterin biosynthesis from GTP, was observed in cerebellum, remaining brain, liver, spleen, and adrenal gland of rats treated with a single dose of lipopolysaccharide (LPS). This led to increased biopterin levels in tissues but not in plasma. Parallel induction of nitric oxide (NO) synthase was indicated by a 10- to 100-fold increase of plasma nitrate levels 6 and 12 hours after injection of LPS. Furthermore, systolic blood pressure was reduced significantly by 23%. Our results demonstrate induction of tetrahydrobiopterin biosynthesis after LPS treatment in vivo.

Animals↗

PubMed1993

Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes.

Push-pull superfusion was used to investigate the release of endogenous GABA in the posterior hypothalamus of the conscious, freely moving rat at basal conditions and in response to centrally applied drugs or to peripherally induced blood pressure changes. After an initial, exponential decline, the release rate of GABA remained fairly constant for many hours. Fluctuations in the release rate of GABA point to the existence of an ultradian rhythm with an approximate frequency of 1 cycle/65 min. Hypothalamic superfusion with a potassium-rich (50 or 90 mmol/l) artificial cerebrospinal fluid led to a concentration-dependent increase in the GABA release. The release of GABA was also enhanced by veratridine (1 or 10 mumol/l) in a concentration-dependent way. Hypothalamic superfusion with the neutrotoxin tetrodotoxin (1 mumol/l) led to a long-lasting decrease in the GABA release. The rise in blood pressure (45 mmHg) elicited by an intravenous infusion of noradrenaline was associated with an increased release rate of GABA in the hypothalamus. Hypotension produced by nitroprusside (25 mmHg) led to a counteracting decrease in hypothalamic GABA outflow. The findings suggest that approximately 45% of the basal outflow of GABA found in the superfusate are released from GABA-ergic neurons of the posterior hypothalamus. The release rate of GABA fluctuates according to an ultradian rhythm. The modified release of GABA in response to experimentally induced blood pressure changes suggests that, in the posterior hypothalamus of the conscious rat, GABAergic neurons are involved in cardiovascular control and possess a hypotensive function.

Animals↗

PubMed1993

Modulation by dopamine receptors of the histamine release in the rat hypothalamus.

The involvement of dopaminergic neurons of the hypothalamus in the modulation of histamine release was studied by the push-pull technique. The posterior hypothalamus of the conscious, freely moving rat was superfused with artificial cerebrospinal fluid (CSF) and the release of histamine was determined radioenzymatically in the superfusate. Agonists and antagonists of dopamine D1-, D2- and D3-receptors were dissolved in CSF and applied to the hypothalamus through the push-pull cannula. Hypothalamic superfusion with the D1-, D2- and D3-receptor agonists dopamine or R(-)-apomorphine enhanced the release rate of histamine. (+/-)-Apomorphine also enhanced the release of histamine, but to a lesser extent than did equimolar concentration of R(-)-apomorphine. The D3-agonist quinpirole inhibited the release of histamine, while the D1-receptor agonist SKF 82958 [(+-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine] did not virtually influence the release of the neurotransmitter. On the other hand, [-]-sulpiride which predominantly blocks D2-receptors, decreased histamine release. Hypothalamic superfusion with SKF 83566 [(+-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine], which seems to be a selective antagonist of D1-receptors, enhanced the release rate of histamine. These findings suggest that dopaminergic neurons of the hypothalamus influence the release of histamine from its neurons in a dual way. D2-heteroreceptors stimulate the release of histamine, while D3-heteroreceptors seem to inhibit the release of this neurotransmitter. Both types of dopamine receptors might be located presynaptically on histaminergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Catecholamine release in the locus coeruleus is modified by experimentally induced changes in haemodynamics.

The involvement of catecholaminergic neurons of the locus coeruleus in central cardiovascular control was investigated in the anaesthetized cat. Push-pull cannulae were bilaterally inserted into the LC and the release of noradrenaline and dopamine was determined radioenzymatically in the superfusate. The effects of experimentally induced changes in blood volume and vascular resistance on catecholamine release in the locus coeruleus were studied. Hypervolaemia strongly inhibited the release of noradrenaline in the locus coeruleus. Intravenous infusion of noradrenaline (5 micrograms.kg-1.min-1) elicited a pronounced pressor response which was also associated with a decrease in the release of noradrenaline in the locus coeruleus. Conversely, a fall of blood pressure caused by a controlled haemorrhage enhanced the release of noradrenaline. A profound fall in blood pressure caused by infusion of nitroprusside (8 micrograms.kg-1.min-1) did not modify the release rate of noradrenaline. Dopamine release rate was not significantly influenced by these cardiovascular alterations. The results demonstrate that increases in blood pressure elicited by vascular constriction or hypervolaemia inhibit the release of noradrenaline in the locus coeruleus. Decreases in blood pressure elicited by hypovolaemia enhance the release of noradrenaline, but lowering blood pressure by vasodilatation is ineffective. Hence, the release of endogenous noradrenaline in the locus coeruleus is responsive to haemodynamic signals, thus supporting the suggested integrative role of the locus coeruleus in central cardiovascular control.

Animals↗

PubMed1993

Pulsatile release of catecholamines in the hypothalamus of conscious rats.

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 20 h. 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.

Activity Cycles↗

PubMed1993

Effects of blood pressure changes on the catecholamine release in the locus coeruleus of cats anaesthetized with pentobarbital or chloralose.

Effects of carotid occlusion and drugs applied intravenously on the release of endogenous catecholamines in the locus coeruleus of cats anaesthetized with pentobarbital or chloralose were investigated. The locus coeruleus was superfused bilaterally with artificial cerebrospinal fluid through push-pull cannulae inserted stereotaxically. Dopamine, noradrenaline and in some experiments also adrenaline were determined radioenzymatically in the superfusate. Under pentobarbital anaesthesia, a bilateral carotid occlusion increased the release rate of noradrenaline in the locus coeruleus, while the release of dopamine was decreased. These changes were due to the fall of blood pressure in the carotid sinus caused by the occlusion. Loading of baroreceptors by elevating blood pressure with phenylephrine (10 micrograms.kg-1 x min-1, i.v. infusion) was accompanied by a decreased release of noradrenaline in the locus coeruleus. This decrease in noradrenaline release was not detected in the caudal aspect of the locus coeruleus. Under chloralose anaesthesia, phenylephrine diminished the release rate of noradrenaline to about the same extent as under pentobarbital anaesthesia. The release rate of adrenaline was also decreased. A prolonged infusion of phenylephrine led to a prolonged pressor response associated with a sustained decrease in the noradrenaline release rate. Intravenous injection of chlorisondamine (3 mg.kg-1) did not change the release of noradrenaline, while dopamine release was reduced. It is concluded that the release of catecholamines in the locus coeruleus is influenced by signals originating from peripheral baroreceptors. The influences are similar under pentobarbital and chloralose anaesthesia. Noradrenergic neurons responding to haemodynamic signals are not uniformly distributed within the locus coeruleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1992

Pulsatile release of histamine in the hypothalamus of conscious rats.

The pattern of histamine release was investigated in the hypothalamus of the conscious, freely moving rat over 20 h. Under anaesthesia, a guide cannula was stereotaxically inserted into the posterior hypothalamus. In the conscious animal, the stylet of the guide cannula was replaced by a push-pull cannula, and the hypothalamus was superfused with artificial cerebrospinal fluid. Histamine was determined radioenzymatically in the superfusate which was continuously collected in time periods of 20 min. The release rate of histamine fluctuated according to an ultradian rhythm (frequency: 1 cycle per 83 min) and a circadian rhythm with the highest release rate of histamine between 11:00 p.m. and 1:00 a.m. The release rate of histamine during darkness was higher than that during the light period. The results demonstrate that, in the brain, neuronal histamine is released according to rhythms with various frequencies.

Animals↗

PubMed1992

Nitric oxide releases acetylcholine in the basal forebrain.

In conscious rats, the basal forebrain was superfused through a push-pull cannula and the release of acetylcholine was determined in the superfusate. Superfusion with the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine, diminished the release of acetylcholine. Subsequent superfusion with the NO donor, 3-morpholino-sydnonimine, enhanced the release of the neurotransmitter. It is concluded that endogenous NO enhances the release of acetylcholine from its neurons.

Acetylcholine↗

PubMed1992

Blood pressure changes modify the release rates of catecholamines in the intermediate nucleus of the solitary tract.

In anaesthetized cats, the intermediate aspect of the nucleus of the solitary tract (NTS) was bilaterally superfused with artificial CSF through push-pull cannulae. The release of the endogenous catecholamines dopamine, noradrenaline and adrenaline was determined in the superfusates radioenzymatically. Blood pressure changes were elicited by intravenous injections of drugs (noradrenaline or chlorisondamine), or electrical stimulation of the intermediate NTS with the tip of the push-pull cannula. Intravenous injections of noradrenaline (3 or 10 micrograms/kg) elicited a rise in the arterial blood pressure which was associated with a decrease in the release rate of adrenaline in the intermediate NTS. The release rates of dopamine and noradrenaline were not influenced. The intravenous injection of chlorisondamine (3 mg/kg) lowered blood pressure and diminished the release rate of dopamine in the intermediate NTS. The release rate of noradrenaline was not modified by chlorisondamine. Electrical stimulation of the intermediate NTS contralateral to the superfused nucleus increased moderately the arterial blood pressure and decreased the release rate of noradrenaline and dopamine, while the release of adrenaline was not influenced. The findings suggest that experimentally induced changes in the arterial blood pressure by drugs injected intravenously modify the release rates of adrenaline and dopamine in the intermediate NTS so as to counteract the blood pressure change. In the intermediate NTS, release of adrenaline from adrenergic nerve terminals seems to act hypertensive. The results obtained with chlorisondamine point to a hypotensive function of endogenous dopamine in the intermediate NTS.

Animals↗

PubMed1992

Effects of gamma-vinyl GABA (vigabatrin) on blood pressure and body weight of hypertensive and normotensive rats.

Inactivation of GABA was inhibited by gamma-vinyl GABA (GVG) and the effects of the increased GABA level in the brain on blood pressure and body weight of spontaneously hypertensive rats (SHR) and normotensive rats (WKY) were investigated. When started at the age of 8 weeks or 5 weeks, treatment of SHR and WKY with GVG (150 mg/kg, s.c.) for several weeks did not influence systolic blood pressure. In 1-week old SHR, treatment with GVG (up to 150 mg/kg, s.c.) abolished the rise in blood pressure until animals were 8 weeks old. Thereafter, arterial blood pressure started to increase but it remained distinctly lower than that in untreated animals. When started at the age of 1 week, treatment with GVG for 7 weeks did not influence arterial blood pressure in WKY. GVG delayed increase in body weight in SHR and WKY, irrespective of their age. GVG greatly increased GABA levels in the hypothalamus, frontal cortex, brainstem and rest of the brain in both WKY and SHR. It is concluded that an increase in the GABA level in the brain leads to a delay in the development of hypertension in young SHR. Hence, development of genetic hypertension seems to be susceptible to activation of the GABAergic system in a very early critical phase only.

4-Aminobutyrate Transaminase↗

PubMed1992

Release of endogenous acetylcholine in the hypothalamus of conscious rats.

The release of endogenous acetylcholine was investigated by the push-pull technique. The posterior hypothalamus of conscious rats was superfused through a push-pull cannula with artificial cerebrospinal fluid (ACSF) which contained 1 mumol/l neostigmine. Acetylcholine was determined in the superfusate by high pressure liquid chromatography and electrochemical detection. Hypothalamic superfusion with potassium-rich (100 mmol/l) ACSF led to a pronounced increase in the release rate of acetylcholine. Tetrodotoxin (1 mumol/l) almost abolished the basal release of the neurotransmitter. Superfusion of the hypothalamus with atropine (10 or 50 mumol/l) led to a concentration-dependent increase, whereas superfusion with oxotremorine (50 mumol/l) inhibited the release rate of acetylcholine. It is concluded that acetylcholine released into the superfusate of the hypothalamus originates from cholinergic neurons. Furthermore, the release of acetylcholine seems to be modulated by muscarinic acetylcholine receptors, probably located on cholinergic neurons of the hypothalamus.

Acetylcholine↗

PubMed1991

Involvement of catecholaminergic neurones of the nucleus of the solitary tract (NTS) in blood pressure regulation.

Determination of the release of catecholamines in the rostral and intermediate aspects of the NTS before, during and after termination of a bilateral carotid occlusion revealed that increases in blood pressure elicited by the occlusion reduce the release rates of noradrenaline and adrenaline, while occlusion-induced decreases in blood pressure diminish the release rate of dopamine. These findings demonstrate that, in response to blood pressure changes elicited by carotid occlusion, in both aspects of the NTS noradrenaline and adrenaline act to increase blood pressure when released from their neurones, while the release of dopamine lowers blood pressure. Noradrenergic neurones of the NTS receive impulses from baroreceptors of carotid sinus and aortic arch.

Animals↗

PubMed1991

In vivo modulation of the histamine release in the hypothalamus by adrenoreceptor agonists and antagonists.

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 alpha 2-agonists noradrenaline or clonidine diminished the release rate of histamine. Moreover, clonidine abolished the potassium-induced increase in the histamine release. Superfusion with the alpha 2-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 alpha 2-adrenoreceptors located on histaminergic nerve terminals.

Adrenergic alpha-Agonists↗

PubMed1991

Release of endogenous catecholamines in two different regions of the nucleus of the solitary tract as influenced by carotid occlusion.

The effects of carotid occlusion on the release of catecholamines in the nucleus of the solitary tract (NTS) were investigated in anaesthetized cats. Two aspects of the nucleus (rostral or intermediate NTS) were superfused bilaterally through push-pull cannulae with artificial CSF and the release of the endogenous dopamine, noradrenaline and adrenaline was determined in the superfusate radioenzymatically. The superfusion rate was 150 microliters/min or 800 microliters/min. In some experiments, superfusion of the intermediate NTS was carried out after denervation of the aortic arch. In the rostral NTS superfused at a rate of 150 microliter/min, bilateral carotid occlusion led to a rise in blood pressure and decreased the release rate of dopamine. These changes continued after occlusion termination. The release rate of noradrenaline was transiently diminished during occlusion. The release of this amine was also decreased after occlusion termination. The release rate of adrenaline was not influenced during carotid occlusion, but it was found to be diminished after termination of the occlusion. Superfusion of the rostral NTS at a rate of 800 microliters/min also reduced the release rate of adrenaline after termination of carotid artery occlusion. In the intermediate NTS (superfusion rate 150 microliters/min) similar effects of the carotid occlusion on the release rates of dopamine and noradrenaline were observed. In this aspect of the NTS, denervation of the aortic arch abolished the decrease in the noradrenaline release during carotid occlusion, while the release rates of dopamine and adrenaline were decreased during and after termination of the carotid occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Does brain histamine contribute to the development of hypertension in spontaneously hypertensive rats?

Histaminergic neurons of the brain have been implicated in genetic hypertension. We investigated the effect of inhibition of histamine synthesis by alpha-fluoromethylhistidine (alpha-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 alpha-fluoromethylhistidine for 29 and 13 days, respectively. Treatment of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats with alpha-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 alpha-fluoromethylhistidine. In young spontaneously hypertensive rats, alpha-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.

Animals↗