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Inactivation pathway of histamine

组胺失活途径

基本信息

批准号：
15590241
负责人：
TAKEMURA Motohiko
金额：
$ 2.37万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

An HPLC system for measurement of histamine and N^T-methylhistamine was constructed as reported by Kasziba et al. with slight modifications. The content of histamine and N^T-methylhistamine in the brain of the rat strain of high ethanol preference (HAP), established by Hishida et al., tended to be larger than those of the rat from low ethanol preference (LAP) strain.When the cortex of HAP was stimulated by histamine in vitro, turnover rate of phosphatidylinositols (PI) was lower than that of LAP. The cortex from mice chronically treated with methamphetamine showed smaller PI turnover rate than that of the control mice. These results suggested that after chronic ethanol or methamphetamine treamtment, activity of histaminergic neurons increases and signal transduction pathway through histamine H_1 receptor-Gq/11-phospholipase C was down-regulated.It was suggested that histaminergic neuron system plays important role in drug dependence, so several drugs were investigated if they can modify increased locomotion, behavioral sensitization, and stereotypic behavior induced by methamphetamine. Clorgyline, a type A monoamine oxidase inhibitor (MAOI), inhibited hyperlocomotion and behavioral sensitization by methamphetamine. It delayed the onset of stereotypic behavior but this effect was not dose-dependent. Selegiline (a type B MAOI) had no effect on hyperlocomotion but increased stereotypic behavior induced by 2-phenylethylamine.Knock-out vector of histamine N^T-methyltransferase was constructed and recombinant embryo was acquired.

Kasziba等人建立了测定组胺和N、T-甲基组胺的高效液相色谱系统。稍加修改。Hishida等建立的高酒精偏爱(HAP)大鼠的脑组织中组胺和N、T-甲基组胺的含量比低乙醇偏爱(LAP)大鼠的脑组织中组胺和N、T-甲基组胺的含量有增加的趋势。长期服用甲基苯丙胺的小鼠大脑皮质的PI周转率比对照组小。这些结果提示，慢性乙醇或甲基苯丙胺处理后，组胺能神经元活性增强，组胺H_1受体-GQ/11-磷脂酶C信号转导通路下调。提示组胺能神经元系统在药物依赖中起重要作用，因此对几种药物是否能改变甲基苯丙胺引起的运动增加、行为敏化和刻板行为进行了研究。Clorgyline是一种A型单胺氧化酶抑制剂(MAOI)，可抑制甲基苯丙胺的多动和行为敏化。它推迟了刻板印象行为的开始，但这种影响不是剂量依赖的。司来吉兰(B型MAOI)对2-苯乙胺诱导的大鼠多动行为无明显影响，但可增加其刻板行为。