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Several physiological functions of 2-arachido.noylglycerol; an endogenous cannabinoid receptor ligand

2-花生酰甘油的几种生理功能

基本信息

批准号：
12680640
负责人：
WAKU Keizo
金额：
$ 1.98万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680640/
关键词：
2-Arachidonoyglycerol Cannabinoid receptor CB2 HL-60 cells MAP kinase Anandamide Chemokine Hypotension 神経伝達血管系

项目摘要

An endogenous cannabimimetic molecule, 2-arachidonoylglycerol, induces a rapid, transient increase in intracellular free Ca^<2+> concentrations in HL-60 cells through a cannabinoid CB2 receptor-dependent mechanism. We examined the activities of a number of relevant compounds (2-arachidonoylglycerol, its structural analogues, and several synthetic cannabinoids). We found that 2-arachidonoylglycerol is the most potent compound examined so far. These results strongly suggested that the cannabinoid CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2-arachidonoylglycerol is the intrinsic physiological ligand for the cannabinoid CB2 receptor which is known to be expressed mainly in the immune system. We also found that 2-arachidonoylglycerol induces the activation of p42/p44 MAP kinases and the enhanced production of kemokines such as IL-8 and MCP-1 in HL-60 cells. These results strongly suggest that 2-arachidonoylglycerol is an important mediator in the immune system, Next, we examined the level of 2-arachidonoylglycerol in the brain isolated from rats injected with picrotoxinin. We found that the level of 2-arachidonoylglycerol was augmented markedly in picrotoxinin-injected rat brain. Similar results were observed with decapitated rat brain. These results suggest that a substantial amount of 2-arachidonoylglycerol was produced in the brain under the condition of stimulation. We confirmed that a large amount of 2-arachidonoylglycerrol was generated rapidly in rat brain homogenate when incubated in the presence of C^<a2+>, We next examined the effect of 2-arachidonoylglycerol on the vascular system. We found that 2-arachidonoylglycerrol induces hypotension in rats. We also found that 2-arachidonoylglycerol enhanced norepinephrine release in isolated rat heart. These results suggest that 2-arachidonoylglycerol is a possible vasomodulator.

内源性拟大麻分子2-花生四烯酸甘油通过大麻素CB 2受体依赖性机制诱导HL-60细胞内游离Ca^2+浓度快速、短暂增加。我们研究了一些相关化合物（2-花生四烯酰甘油，其结构类似物和几种合成大麻素）的活性。我们发现，2-花生四烯酰甘油是迄今为止最有效的化合物。这些结果强烈地表明，大麻素CB 2受体最初是2-花生四烯酸酰甘油受体，并且2-花生四烯酸酰甘油是大麻素CB 2受体的固有生理配体，已知大麻素CB 2受体主要在免疫系统中表达。我们还发现，2-花生四烯酸甘油诱导HL-60细胞中p42/p44 MAP激酶的激活和增强的趋化因子如IL-8和MCP-1的产生。这些结果有力地表明，2-花生四烯酸甘油是免疫系统中的重要介质。接下来，我们检查了从注射印防己毒素的大鼠分离的脑中的2-花生四烯酸甘油的水平。我们发现，2-花生四烯酸甘油的水平显着增加，在印防己毒素注射大鼠脑。用断头大鼠脑观察到类似的结果。这些结果表明，在刺激条件下，脑中产生大量的2-花生四烯酸甘油。我们证实，当在C^<a2+>存在下孵育时，在大鼠脑匀浆中迅速产生大量的2-花生四烯酸酰甘油。我们接下来检查了2-花生四烯酸酰甘油对血管系统的作用。我们发现，2-花生四烯酸甘油诱导大鼠低血压。我们还发现，2-花生四烯酸甘油增强去甲肾上腺素释放在离体大鼠心脏。这些结果表明，2-花生四烯酸甘油是一种可能的血管调节剂。