Modulation of histamine release in the hypothalamus by nitric oxide

Inflammation Research -     

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

To investigate whether histamine receptor ligands influence thein 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)-α-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 incresing 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.

     

Modulation of acetylcholine release in the ventral striatum by histamine receptors

Inflammation Research -     

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

Summary 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 g·kg^–1·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. It is suggested that noradrenergic and possibly dopaminergic and adrenergic neurons of the locus coeruleus are involved in the baroreceptor reflex, thus contributing to central homeostasis of blood pressure.     

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

To investigate whether histamine receptor ligands influence thein 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)--methylhistamine was ineffective. The results indicate that H₁ receptors and H₃ receptors modulate acetylcholine release.     

Influence of NOS inhibitors on changes in ACH release and NO level in the brain elicited by amphetamine neurotoxicity

We studied the possible role of neurotoxicity in the d,l-amphetamine (AMPH)-induced release of acetylcholine (ACH) in the nucleus accumbens (Nac) and the involvement of endogenous NO in this process. For determination of ACH release the Nac was superfused using the push-pull-technique. NO was directly measured using the electron paramagnetic resonance technique. Repeated administration of AMPH increased ACH release by about 400%. N-nitro-L-arginine (L-NNA) and 7-nitroindazole (7-NI) nearly abolished the AMPH-induced increase in ACH release. AMPH increased NO as well as lipid peroxidation (LPO) products in the cortex. L-NNA and 7-NI substantially diminished NO increase. AMPH-evoked LPO was only slightly reduced by these compounds. It is concluded that AMPH enhances ACH release through increased NO synthesis and induces neurotoxicity via NO and by LPO independent NO generation.     

Release of serotonin in the locus coeruleus of normotensive and spontaneously hypertensive rats (SHR)

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. Received: 16 November 1998 / Accepted: 22 February 1999     

Effects of local MAO inhibition in the locus coeruleus on extracellular serotonin and 5-HIAA during exposure to sensory and cardiovascular stimuli

Previously, we have shown that in the presence of pargyline the release of serotonin (5-HT) in the locus coeruleus is modulated by various sensory stimuli and blood pressure fluctuations. The aim of the present study was to investigate whether local inhibition of monoamine oxidase (MAO) influences basal and stimulus-induced release of 5-HT in the locus coeruleus. For this purpose, the locus coeruleus was superfused in the absence and in the presence of the MAO inhibitor pargyline. Additionally, we examined whether the release of the 5-HT metabolite 5-hydroxy-indole acetic acid (5-HIAA) in the locus coeruleus is altered in response to stimuli. The locus coeruleus of the conscious rat was superfused through a push-pull cannula with artificial cerebrospinal fluid (CSF). 5-HT and 5-HIAA were determined in the superfusate. The basal release rate of 5-HT and the basal outflow of 5-HIAA averaged 2.0 fmol/min and 69 fmol/min, respectively. The basal release rate of 5-HT and the 5-HIAA outflow were tetrodotoxin (TTX)-sensitive. In the absence of pargyline, the sensory stimuli noise stress or tail pinch, applied for 10 min, increased 5-HT and 5-HIAA outflow by 50–70%. In contrast, an experimentally induced rise in blood pressure for 10 min enhanced 5-HT release by 50%, but had no effect on 5-HIAA outflow. The release of 5-HT and/or 5-HIAA elicited by sensory stimuli or a blood pressure rise was abolished by TTX. Addition of pargyline to the CSF enhanced 5-HT release fourfold and slightly decreased 5-HIAA outflow. These levels remained stable throughout the entire observation period of 8 h. In the presence of pargyline, 5-HT release elicited by noise, tail pinch and increase in blood pressure was enhanced. It is concluded that superfusion with pargyline enhances 5-HT release and reduces 5-HIAA outflow in the locus coeruleus. Furthermore, the ability of sensory stimuli and baroreceptor activation to enhance 5-HT release is preserved during a prolonged pargyline-induced increase in extracellular 5-HT. Since sensory stimuli enhanced, while baroreceptor activation did not influence 5-HIAA outflow, 5-HIAA is not a reliable index for short-term changes in the activity of serotonergic neurons in the locus coeruleus. Received: 13 July 1998 / Accepted: 10 December 1998     

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

Summary 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 l/min or 800 l/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 l/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 l/min also reduced the release rate of adrenaline after termination of carotid artery occlusion. In the intermediate NTS (superfusion rate 150 l/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 carotic occlusion, while the release rates of dopamine and adrenaline were decreased during and after termination of the carotid occlusion.The results suggest that (a) the rise in blood pressure in the carotid sinus after termination of a carotid occlusion decreases the release rates of noradrenaline and adrenaline in the NTS, (b) the decrease in the release of noradrenaline during carotid occlusion is due to impulses originating from the baroreceptors of the aortic arch.Thus, impulses from carotid sinus and aortic arch modify the release rates of noradrenaline in the NTS so as to counteract blood pressure changes.Supported by the Fonds zur Förderung der wissenschaftlichen Forschung Send offprint requests to A. Philippu at the above address     

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

Summary Inactivation of GABA was inhibited by -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. Send offprint requests to N. Singewald at the above addressThis work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung