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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，本研究用荧光显微镜观察了大鼠脑内内源性组胺的动态变化。透析法以下-是研究成果的总结。（1）下丘脑前区组胺的释放对河豚毒素敏感，依赖于细胞外钙离子，并可被组胺能胞体和神经末梢的去极化刺激所增强，表明所观察到的释放是神经元源性的。（2）释放量有明显的昼夜变化，暗期高，明期低。（3）GABA或谷氨酸经透析膜给药时，释放分别受到抑制和增强。进一步的神经化学研究表明，谷氨酸释放的增强作用是由位于组胺能神经末梢的突触前NMDA受体介导的。（4）电刺激结节乳头核可增加海马内源性乙酰胆碱的释放。腹腔注射组胺合成抑制剂α-氟甲基组氨酸或脑穿透性组胺H2受体阻断剂唑兰替丁可抑制电诱发的乙酰胆碱释放。硫代哌丁胺通过阻断突触前自身受体H3受体而促进组胺释放，使基础乙酰胆碱释放显著增加。这一结果表明，位于内侧隔的胆碱能神经元的活动受到组胺能系统的调节。（5）前庭刺激可使下丘脑前区组胺释放增加，提示中枢组胺能系统可能参与了运动病的前庭自主反射。