Physiological significance of the histaminergic system : A brain microdialysis study using unanesthetized and freely-moving rats

组胺能系统的生理意义：使用未麻醉且自由活动的大鼠进行脑微透析研究

基本信息

批准号：
02670085
负责人：
YAMATODANI Atsushi
金额：
$ 1.47万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

To elucidate physiological significance and its neurochemical mechanisms of the central histaminergic neuron system, I examined dynamics of endogenous histamine in the rat brain using a mier. odialysis method. The- following. are the summary of research results.(1)Histamine release from the anterior hypothalamic area was sensitive to tetorodotoxin and dependent on extracellular calcium, and was enhanced by depolarization stimuli of the histaminergic cell bodies and nerve terminals, indicating that the observed release was of neuronal origin.(2)The release had a clear eircadian variation being high in dark period and low in light period.(3)When GABA or glutamic acid was administered through the dialysis membrane, the release was suppressed and enhanced, respectively. Further neurochemical studies revealed that the enhancement of the release by glutamic acid was mediated by presynaptic NMDA receptors located on histaminergic nerve terminals.(4)The release of endogenous acetylcholine from the hippocampus was increased by electrical stimulation on the tuberomammillary nucleus where the histaminergic cell bodies were confined. The electrically evoked acetylcholine release was suppressed by int raperitoneal administration of alpha-fluorometylhistidine, a s pe c if i c inhibitor of histamine synthesis or zolantidine, a- brain-penetrating histamine H2receptor blocker. The basal acetylcholine release was significantly increased by thioperamide administration, which enhanced the histamine release by blocking presynaptic autoreceptor, H3-receptor. This result indicates that activity of the cholinergic neurons located in the medial septum is regulated by the histaminergic system.(5)Histamine release from the anterior hypothalamic area was increased by vestibular stimulation indicating possible participation of the central histaminergic system in the vestibular-autonomic reflex of motion sickness.

为了阐明中枢组胺能神经元系统的生理意义及其神经化学机制，我使用米尔检查了大鼠大脑中内源性组胺的动态。透析法。下列。 (1)下丘脑前区释放的组胺对河豚毒素敏感，依赖于细胞外钙，并受到组胺能细胞体和神经末梢去极化刺激的增强，表明观察到的释放是神经元的释放。 (2)释放量具有明显的昼夜变化，黑暗期高，光照期低。(3)当通过透析给予GABA或谷氨酸时膜上，释放分别受到抑制和增强。进一步的神经化学研究表明，谷氨酸释放的增强是由组胺能神经末梢上的突触前NMDA受体介导的。(4)电刺激组胺能细胞体所在的结节乳头核，可增加海马内源性乙酰胆碱的释放。被限制了。通过腹膜内施用α-氟甲基组氨酸（组胺合成的特异性抑制剂）或唑兰替丁（α-脑穿透组胺H 2 受体阻断剂）来抑制电诱发的乙酰胆碱释放。硫哌丁胺给药显着增加基础乙酰胆碱释放，通过阻断突触前自身受体 H3 受体来增强组胺释放。这一结果表明，位于内侧隔膜的胆碱能神经元的活动受到组胺能系统的调节。(5)前庭刺激使下丘脑前区的组胺释放增加，表明中枢组胺能系统可能参与前庭自主反射。晕车。