2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist

2-花生四烯酰甘油，一种内源性大麻素受体激动剂

• 批准号: 09680631
• 负责人: SUGIURA Takayuki
• 金额: $ 2.05万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680631/
• 关键词: cannabinoid; 2-arachidonoylglycerol; arachidonic acid; neuromodulator; anandamide; inositol phospholipids; 2-アラキドノイルグリセロール; イノシトールリン脂酸; アラキドノイルグリセロール; モノグリセリド

An endogenous carmabimimetic molecule, 2-arachidonoylglycerol, induces a rapid, transient increase in intracellular free Ca^<2+> concentrations in NG1O8-15 cells through a cannabinoid CB1 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. We confirmed that a metabolically stable ether-linked analogue of 2-arachidonoylglycerol possesses appreciable agonistic activity, although its activity was apparently lower than that of 2-arachidonoylglycerol. These results strongly suggested that the cannabinoid CB1 receptor is originally a 2-arachidonoylglycerol receptor, and 2-arachidonoylglycerol is the intrinsic physiological ligand for the cannabinoid CB1 receptor.Next we examined the molecular species compositions of monoacyiglycerols obtained from various rattissues by reverse-phase HPLC and GC-MS analyses. We confirmed that 2-arachidonoylglycerol, an endogenous cannabinoid receptor agonist, is one of most abundant molecular species of monoacylglycerols in the brain. Substantial amounts of 2-arachidonoylglycerol were also found in liver, spleen, lung and kidney. We also found that human endothelial cells produce 2-arachidonoylglycerol when stimulated with thrombin. We confirmed that human vascular smooth muscle cells possesses the cannabinoid CB1 receptor mRNA.It is possible, therefore, that 2-arachidonoylglycerol, an endogenous cannabinoid receptor agonist, is a possible vasomodulator.

内源性carmabimetic分子，2-芳基烯丙基甘油，通过大麻素CB1受体依赖性机制在NG1O8-15细胞中诱导NG1O8-15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。我们证实，尽管其活性显然低于2-芳基二烯丙基甘油的活性，但2-芳基烯丙基甘油的代谢稳定的醚连接类似物具有明显的激动活性。 These results strongly suggested that the cannabinoid CB1 receptor is originally a 2-arachidonoylglycerol receptor, and 2-arachidonoylglycerol is the intrinsic physiological ligand for the cannabinoid CB1 receptor.Next we examined the molecular species compositions of monoacyiglycerols obtained from various rattissues by reverse-phase HPLC and GC-MS分析。我们证实，2-芳基酮甘油是一种内源性大麻素受体激动剂，是大脑中最丰富的单酰基甘油的分子种类之一。在肝脏，脾，肺和肾脏中也发现了大量2-芳基烯丙基甘油。我们还发现，当用凝血酶刺激时，人内皮细胞会产生2-芳基酮甘油。我们证实人血管平滑肌细胞具有大麻素CB1受体mRNA。因此，可能是一种可能的血管瘤剂。

项目成果

Dimargo,V.et al.: "The novel endogenous cannabinoid 2-arachidonoylglycerolis inacti vated by neuronal-and basophil-like cells" Biochem.J.331. 15-19 (1998)

Dimargo,V.等人：“神经元和嗜碱性粒细胞样细胞灭活的新型内源性大麻素 2-花生四烯酰甘油”Biochem.J.331。

Sugirura, T., Kodaka, T., Kondo, S.et al.: "Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor?" J.Biochem.122. 890-895 (1997)

Sugirura, T.、Kodaka, T.、Kondo, S.等人：“大麻素 CB1 受体是 2-花生四烯酰甘油受体吗？”

Sugiura, T., Kodaka, T., Nakane, S.et al.: "Detection of an endogenous cannabimimetic molecules, 2-arachidonoylglycerol" Biochem.Biophys.Res.Commun.243. 838-843 (1998)

Sugiura, T.、Kodaka, T.、Nakane, S.等人：“内源性大麻模拟分子 2-花生四烯酰甘油的检测”Biochem.Biophys.Res.Commun.243。

Sugiura, T., Kodaka, T., Kondo, S.et al.: "Anandamide and 2-arachidonoylglycerol (in Japanese)" Saiboukougaku. 17. 746-753 (1998)

Sugiura, T.、Kodaka, T.、Kondo, S.等人：“Anandamide 和 2-arachidonoylglycerol（日语）”Saiboukougaku。