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.

     

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.     

Modulation of acetylcholine release by histamine in the nucleus accumbens

Inflammation Research -     

Histaminergic H2 receptor ligands modulate acetylcholine release in the ventral striatum

Inflammation Research -     

Modulation of histamine release in the hypothalamus by nitric oxide

Inflammation Research -     

Modulation of lysophosphatidylserine-dependent histamine release

Apomorphine (2–30 M) inhibits lysophosphatidyl-serine-dependent histamine release in rat and mouse peritoneal mast cells. The drug-induced inhibition is influenced by the concentration of lysophosphatidylserine. Log concentration-response curves show a surmountable type of antagonism between the two compounds.     

Modulation by S-adenosyl-methionine and S-adenosyl-homocysteine of the human leucocytes histamine release

Methylation of membrane phospholipids is an important stage in the process of histamine release. This methylation reaction can be modulated by S-adenosyl-methionine (SAM) as well as by S-adenosyl-homocysteine (SAH). The influence of SAM and of SAH upon the histamine release of leucocytes from asthmatic and normal subjects were compared. In concentration of 10^-4M, SAM enhanced spontaneous and the specifically induced histamine release. In concentration of 10^-5 M SAM enhanced the histamine release only in normals. This phenomenon could indicate a deficit in methyl-transferase activity in the asthamatics. In concentration of 10^-4 M, SAH reduced spontaneous and specifically induced histamine release, having an effect comparable to that of 10^-4 M Theophylline.     

Modulation of the spontaneous histamine release by adrenergic and cholinergic drugs

Experiments have been reported on the possible modulation of the spontaneous histamine release by adrenergic and cholinergic drugs.Adrenergic drugs increase the spontaneous histamine release in vivo, and in neoplastic mast cells, in vitro. The mechanism of histamine release appears to be dependent upon the activation of alpha-adrenoceptors.Cholinergic drugs activate the release of histamine in many secretory processes in vivo; in vitro, acetylcholine is one of the most powerful histamine releasers in isolated purified rat mast cells.The release of histamine evoked by acetylcholine in rat mast cells is a calcium-requiring, temperature-dependent exocytosis. The physiological relationship of the sympathetic, parasympathetic and histamine-containing cells are discussed.Lecture held at the Sixth Annual Meeting of the European Branch of the Histamine Club, London, April 20–22, 1977.     

肝素对人肥大细胞组胺分泌的调节作用

目的　研究肝素对人肥大细胞组胺释放的影响。方法　经酶消化后的肺和扁桃体组织的细胞成份同肝素、抗人IgE抗体或钙离子导入剂共同培养 ,以特制的纤维玻璃为基础的方法测量组胺。结果　经 15和 4 5min培养 ,肝素对人肺和扁桃体组织肥大细胞组胺释放无明显影响。而将肝素与抗IgE抗体同时加入酶悬浮的肺肥大细胞中 (预培养时间为 0min) ,肝素可抑制 5 0 %的抗IgE抗体诱导的组胺释放 ,且抑制率与肝素浓度呈正相关。肝素对抗IgE抗体引起的扁桃体肥大细胞的组胺释放无抑制作用 ,对钙离子导入剂诱导的肺和扁桃体的肥大细胞组胺释放无明显影响。结论　本实验首次发现肝素可以抑制抗IgE抗体诱导的人肺肥大细胞组胺释放 ,因此在肺部的变态反应性炎症中可能起到一定的预防和治疗作用     

H3 Autoreceptors and muscarinic acetylcholine receptors modulate histamine release in the anterior hypothalamus of freely moving rats

To investigate the modulation of histamine release by autoreceptors and heteroreceptors, the rat anterior hypothalamus was superfused through a push-pull cannula with agonists or antagonists of histamine and acetylcholine muscarinic receptors. Superfusion with the H₃ receptor agonist (R)-α-methylhistamine inhibited, while superfusion with thioperamide (H₃ antagonist) enhanced histamine release. Superfusion with carbachol (a mixed M₁, M₂, M₃ agonist) inhibited the release of histamine. The release of endogenous histamine was enhanced on superfusion with atropine (a mixed M₁, M₂, M₃ antagonist). The M₃ muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine enhanced the release rate of histamine. It is concluded that in the anterior hypothalamus the release of endogenous histamine is modulated by H₃ autoreceptors. Moreover, acetylcholine released from cholinergic neurons also modulates the release of histamine via M₁ and/or M₃ heteroreceptors.

     

Modulation of anaphylactic histamine release by calcium channel agonists and antagonists

Calcium antagonists have been reported to exert protective effects in hypersensitivity reactions in man and animals. However, their effect on anaphylactic histamine release is highly variable and controversial. In the present paper we evaluate the effect of calcium entry blockers and BAY K 8644 on the response to specific antigen in isolated hearts taken from actively sensitized guinea-pigs and from isolated rat and guinea-pig mast cells, actively or passively sensitized. Verapamil, diltiazem, nifedipine and prenylamine dose-dependently decreased anaphylactic histamine release in isolated actively sensitized guinea-pig mast cells. BAY K 8644 was found to be ineffective. In isolated, passively sensitized rat mast cells, verapamil showed a highly signficant inhibitory effect, while prenylamine (10^–4 M) was able to evoke a histamine releasing effect. In cardiac anaphylaxis verapamil, diltiazem, prenylamine, but not nifedipine, were active in reducing the release of histamine without modifying the antigen-induced arrhythmias and positive chronotropic and inotropic effects.     

Comparison of basophil histamine release induced by the cross-linking of IgE receptors

Basophil histamine release induced by allergens (house dust and Candida albicans) and anti-IgE was examined in 31 patients with bronchial asthma in relation to patient age, age at onset of the disease and serum IgE levels. Basophils from patients under 40 years of age generally released a significantly large amount of histamine by stimulation with house dust and anti-IgE. On the other hand, histamine release from patients over 41 years of age was generally not marked when the cells were incubated with house dust and anti-IgE, although, in some cases, the release induced by C. albicans was fairly marked. Basophils from patients under 30 years of age at onset were reactive to house dust and anti-IgE, while the cells from patients over 41 years of age at onset tended to be reactive only to C. albicans. Basophils from patients with low serum IgE levels were less reactive than the cells from patients with high levels of IgE to house dust and anti-IgE. C. albicans-induced release of histamine did not correlate with serum IgE levels.     

Modulation of GABA release by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and N-methyl-D-aspartate receptors in matrix-enriched areas of the rat striatum.

Using a new in vitro superfusion device, the release of preloaded [3H]GABA was examined in microdiscs of tissues taken from sagittal slices in matrix-enriched areas of the rat striatum. Potassium (9 mM, 15 mM) stimulated the release of [3H]GABA in a concentration- and calcium-dependent manner and the veratridine (1 microM)-evoked release of [3H]GABA was completely abolished in the presence of tetrodotoxin (1 microM). The selective glutamatergic agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM) enhanced the potassium-evoked release of [3H]GABA as well as the basal outflow of [3H]GABA. This latter effect was found to be calcium-dependent, partially diminished by tetrodotoxin (1 microM), completely blocked by 6,7-dinitro-quinoxaline-2,3-dione (0.1 mM), which is generally used as an antagonist of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors, but not affected by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801, 10 microM), a specific antagonist of N-methyl-D-aspartate receptors. Similarly, N-methyl-D-aspartate (1 mM) enhanced both the potassium (9 mM) and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM)-evoked release of [3H]GABA but when used alone, due to the presence of magnesium in the superfusion medium, was ineffective on the basal efflux of [3H]GABA. A stimulatory effect of N-methyl-D-aspartate (1 mM) on the basal outflow of [3H]GABA was observed, however, when magnesium was omitted from the superfusion medium. The stimulatory effect of N-methyl-D-aspartate (1 mM) observed in the presence of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate was not potentiated by glycine (1 microM, in the presence of strychnine 1 microM) and the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was not enhanced by D-serine (1 mM), suggesting that endogenous glycine is already acting on N-methyl-D-aspartate receptors. In fact, in the absence of magnesium, 7-chloro-kynurenate (1 mM) completely abolished the stimulatory effect of N-methyl-D-aspartate on the release of [3H]GABA confirming that under our conditions, the glycine site of the N-methyl-D-aspartate receptor is saturated. N-methyl-D-aspartate-evoked responses were all blocked by MK801 (10 microM). Finally, the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was markedly reduced in the presence of tetrodotoxin (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)     

Modulation of morphine state-dependent learning by muscarinic cholinergic receptors of the ventral tegmental area

In the present study, the effects of bilateral intra-ventral tegmental area (intra-VTA) injections of an anticholinesterase, physostigmine and/or muscarinic acetylcholine receptor antagonist, atropine on memory retention and morphine state-dependent learning were examined in adult male Wistar rats. As a model of learning, a step-through passive avoidance task was used. Post-training subcutaneous administration of morphine (0.5, 2.5 and 5 mg/kg) dose-dependently impaired memory retrieval on the test day. Pre-test administration of morphine (2.5 and 5 mg/kg) induced state-dependent retrieval of the memory acquired under post-training morphine influence. Pre-test intra-VTA microinjection of physostigmine (0.5, 1 and 2 microg/rat) or atropine (1, 2 and 3 microg/rat) alone cannot affect memory retention. Interestingly, pre-test intra-VTA administration of physostigmine (1 and 2 microg/rat) reversed post-training morphine (5 mg/kg, s.c.)-induced retrieval impairment. Furthermore, pre-test intra-VTA microinjection of physostigmine (1 and 2 mug/rat) with an ineffective dose of morphine (0.5 mg/kg), synergistically improved memory performance impaired by post-training morphine. On the other hand, pre-test intra-VTA microinjection of atropine (2 and 3 microg/rat) 5 min before the administration of morphine (5 mg/kg, s.c.) dose-dependently inhibited morphine state-dependent memory. Pre-test atropine microinjection also reversed the influence of physostigmine on morphine response. It may be concluded that the muscarinic acetylcholine receptors of the VTA play an important role in morphine-induced recovery of memory, on the test day.     

Modulation of histamine release by rat peritoneal mast cells in a superfusion set-up

A new method is presented for studying mediator release in isolated peritoneal cells of the rat. Using a superfusion technique, cells can be maintained in a continuously cleared medium. Cells were stimulated with antigen, compound 48/80 or A23187 to characterize this preparation. In addition, inhibitory effects of theophylline, isoprenaline and cromoglycate on compound 48/80-induced histamine release were studied. We conclude that superfusion is a valid alternative to study mediator release from isolated peritoneal cells.     

Modulation of taurine release by glutamate receptors and nitric oxide

Taurine is held to function as a modulator and osmoregulator in the central nervous system, being of particular importance in the immature brain. In view of the possible involvement of excitatory pathways in the regulation of taurine function in the brain, the interference of glutamate receptors with taurine release from different tissue preparations in vitro and from the brain in vivo is of special interest. The release of taurine from the brain is enhanced by glutamate receptor agonists. This enhancement is inhibited by the respective receptor antagonists both in vitro and in vivo. The ionotropic N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor agonists appear to be the most effective in enhancing taurine release, their effects being receptor-mediated. Kainate is less effective, particularly in adults. Of the glutamate receptors, the NMDA class seems to be the most susceptible to modulation by nitric oxide. Nitric oxide also modulates taurine release, enhancing the basal release in both immature and mature hippocampus, whereas the K(+)-stimulated release is generally inhibited. Metabotropic glutamate receptors also participate in the regulation of taurine release, group I metabotropic glutamate receptors potentiating the release in the developing hippocampus, while group III receptors may be involved in the adult. Under various cell-damaging conditions, including ischemia, hypoxia and hypoglycemia, taurine release is enhanced, together with an enhanced release of excitatory amino acids. The increase in extracellular taurine upon excessive stimulation of glutamate receptors and under cell-damaging conditions may serve as an important protective mechanism against excitotoxicity, being particularly effective in the immature brain.     

Involvement of dopamine D(2) receptors in complex maze learning and acetylcholine release in ventral hippocampus of rats

In the current study we focus on the involvement of dopamine D(2) receptors in the ventral hippocampus in memory performance and acetylcholine release. Using the aversively motivated 14-unit T-maze (Stone maze) the injection of raclopride, a D(2) receptor antagonist, into the ventral hippocampus (8 microg/kg) was found to impair memory performance. Co-injection of quinpirole, a D(2) receptor agonist (8 microg/kg), overcame the impairment in performance. Microdialysis study revealed that quinpirole infusion (10-500 microM) into the ventral hippocampus stimulated acetylcholine release in a dose-dependent manner, and systemic injection of quinpirole (0.5 mg/kg, i.p.) also stimulated acetylcholine release in the ventral hippocampus. Infusion of eticlopride, another D(2) receptor antagonist, into the ventral hippocampus suppressed acetylcholine release in the hippocampus induced by systemic injection of quinpirole. Taken together, we suggest that D(2) receptors in the ventral hippocampus are involved in memory performance, possibly through the regulation of acetylcholine.     

Modulation of IgE-mediated histamine release from human leukocytes by a new class of histamine H2-agonists

A new class of phenyl (pyridylalcyl) guanidines, acting as potent histamine H₂-agonists, inhibits IgE-mediated human basophil histamine release in a nanomolar range. IC₃₀-level of three substitutes of this group (arpromidine, BUA-75, and FRA-19) were found to be 0.02, 0.015 and 0.008 M. The inhibition appeared with a fast onset (plateau after 10 min. preincubation) and claimed its maximum (60±2.9%, 63±1.8%, and 61±3.1%,n=7) with 10 M of the compounds. H₂-mediated inhibition was totally blocked by 10 M famotidine, a potent histamine H₂-antagonist. The amount of anti-IgE or antigen for the initiation of the immunological release influenced the strength of inhibition of H₂-agonist FRA-19 (p<0.05). Combined preincubation of FRA-19 with zardaverine, a cAMP-specific phosphodiesterase III/IV inhibitor, produced a synergistical inhibitory effect of leukocyte histamine release, which might explained by their different sites of action on intracellular cAMP levels. The capability of histamine to inhibit its own release is mediated by H₂-receptors exclusively. New, potent H₂-receptor stimulating compounds with positive inotropic effects possess additional potent anti-allergic properties.This work was supported by grant K1 622/1-1 from the Deutsche Forschungsgemeinschaft.     

Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats

The effect of acetyl-L-carnitine (ALC) on the spontaneous release of acetylcholine (ACh) in the striatum and hippocampus of freely moving rats was investigated using brain microdialysis coupled with HPLC-electrochemical detection. Systemic administration of ALC, in a dose-dependent manner, stimulated ACh release in both areas, while the D-enantiomer was substantially ineffective. The effect of ALC was strongly Ca2+ dependent and tetrodotoxin (TTX) sensitive. These features of an exocytotic and impulse flow-dependent mechanism suggest that the increase in ACh release is the result of ALC activation of a physiological mechanism in cholinergic neurons.