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.

内源性大麻分子，2-芳基烯丙基甘油，通过大麻素CB2受体依赖性机制诱导HL-60细胞中细胞内游离Ca^<2+>浓度的快速瞬时增加。我们检查了许多相关化合物的活性（2-芳基烯丙基甘油，其结构类似物和几种合成大麻素）。我们发现，2-芳基烯丙基甘油是迄今为止检查的最有效的化合物。这些结果强烈表明，大麻素CB2受体最初是一种2-芳基烯丙基甘油受体，而2-芳基二烯丙基甘油是大麻素CB2受体的固有生理配体，该生理配体在免疫系统中主要表达。我们还发现，2-芳基烯丙基甘油诱导p42/p44 MAP激酶的激活以及在HL-60细胞中IL-8和MCP-1等Kemokines的产生增强。这些结果强烈表明，2-芳基酮甘油是免疫系统中的重要介体，接下来，我们检查了从注射的大鼠细菌毒素中分离出的大脑中的2-芳基酮甘油。我们发现，2-芳基烯丙基甘油的水平在注入picrotoxin的大鼠脑中显着增强。用斩首的大鼠脑观察到了相似的结果。这些结果表明，在刺激的条件下，在大脑中产生了大量的2-芳基烯丙基甘油。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了大量的2-芳基烯丙基甘油酚，接下来我们检查了2-芳基二烯丙基甘油对血管系统的影响。我们发现2-芳基烯丙基糖酚会诱导大鼠的低血压。我们还发现，2-芳基烯丙基甘油在分离的大鼠心脏中增强了去甲肾上腺素的释放。这些结果表明，2-芳基烯丙基甘油是可能的血管调节剂。