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MIER检查了大鼠脑中内源性组胺的动力学。 odiasis方法。下列。是研究结果的摘要。（1）从前下丘脑区域释放组胺对二毒素敏感并依赖于细胞外钙，并通过组胺能细胞体的去极化刺激增强（3）当通过透析膜施用GABA或谷氨酸时，分别抑制和增强了释放。进一步的神经化学研究表明，谷氨酸释放的增强是通过突触前NMDA受体介导的，位于组胺能神经末端上。（4）内源性乙酰胆碱从海马中释放的释放是通过对纤维乳核酸核细胞的电蛋白细胞的电刺激性的，而在海马中增加了hippocampus。如果IC组胺合成抑制剂或Zolantidine，A-脑穿透脑渗透组胺H2RECEPTOR BLOCKEBEPTOR BLOCKER抑制剂，则通过int raperitoneal给药抑制了电诱发的乙酰胆碱的释放，即S PE C抑制乙酰胆碱。硫代酰胺给药可显着增加基底乙酰胆碱的释放，从而增强了组胺释放，通过阻断突触前自身受体H3受体受体。该结果表明，位于内侧隔膜中的胆碱能神经元的活性受组蛋白能系统的调节。（5）通过前庭刺激增加了从下丘脑前区域中的组胺释放，表明中枢组胺能参与前庭 - 运动系统中中央组成症的可能参与。