Physiological roles of 2-arachidonoylglycerol in the nervous system and the immune system

2-花生四烯酰甘油在神经系统和免疫系统中的生理作用

• 批准号: 14580653
• 负责人: WAKU Keizo
• 金额: $ 2.3万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580653/
• 关键词: Cannabinoid; 2-Arachidonoylglycerol; Anandamide; CB1 Receptor; CB2 Receptor; Glutamic acid; Chemokine; Chemotaxis; アラキドン酸; 小脳スライス; アクチン重合; 炎症・免疫; ナチュラルキラー細胞; グルタミン酸放出; リゾホスファチジルイノシトール; リゾホスファチジン酸

1. The generation of 2-AG in the brain was first examined. In this study, we examined the synthesis of 2-AG in rat brain slices, We found that the level of 2-AG was augmented markedly in depolarized rat brain slices. The generation of 2-AG was also observed in glutamate-stimulated brain slices. We also found that treatment of synaptosomes with SR141716A significantly enhanced the release of glutamate from synaptosomes upon depolarization. These results strongly suggest that 2-AG released from stimulated neurons may have an important physiological role in the attenuation of synaptic transmission by acting on the CB1 receptor expressed. primarily in the presynapse2. Physiological roles of 2-AG in inflammation was next examined. We found that 2-AG induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes. The 2-AG-induced migration of HL-60 cells was markedly reduced when the cells were pretreated with either SR 144528 or PTX, suggesting that the migration was mediated through the CB2 receptor and Gi/Go. The 2-AG-induced migration was also observed with KHYG-1 human natural killer cells and human peripheral blood natural killer cells. We also found that the addition of 2-AG to HL-60 cells enhanced the production of chemokines such as IL-8 and MCP-1 through a CB2 receptor-and Gi/Go-dependent mechanism. Finally, we examined the generation of 2-AG at the site of inflammation. We found that the level of 2-AG was markedly elevated in mouse peritoneal cavity injected with carrageenan. These results strongly suggest that 2-AG has a stimulative rather than suppressive role during inflammatory reactions and immune 1 responses

1. 首先检测脑内2-AG的生成。在本研究中，我们检测了大鼠脑切片中2-AG的合成，我们发现在去极化的大鼠脑切片中2-AG的水平明显增加。在谷氨酸刺激的脑切片中也观察到2-AG的产生。我们还发现用SR141716A处理突触体可以显著增强突触体去极化时谷氨酸的释放。这些结果强烈提示，受刺激神经元释放的2-AG可能通过作用于CB1受体的表达，在突触传递的衰减中具有重要的生理作用。主要在突触前。接下来研究2-AG在炎症中的生理作用。我们发现2-AG诱导HL-60细胞向巨噬细胞样细胞和人外周血单核细胞的迁移。SR 144528或PTX预处理后，2- ag诱导的HL-60细胞迁移能力明显减弱，表明迁移是通过CB2受体和Gi/Go介导的。KHYG-1人自然杀伤细胞和人外周血自然杀伤细胞也观察到2- ag诱导的迁移。我们还发现，在HL-60细胞中添加2-AG可以通过CB2受体和Gi/ go依赖机制增强IL-8和MCP-1等趋化因子的产生。最后，我们检测了炎症部位2-AG的生成。我们发现卡拉胶注射后小鼠腹腔2-AG水平明显升高。这些结果强烈提示2-AG在炎症反应和免疫反应中具有刺激作用而不是抑制作用

项目成果

Atsushi Yamashita et al.: "Reverse Reaction of Lysophosphatidylinositol Acyltransferase."J.Biol.Chem.. 278. 30382-30393 (2003)

Atsushi Yamashita 等：“溶血磷脂酰肌醇酰基转移酶的逆反应”。J.Biol.Chem. 278. 30382-30393 (2003)

Takayuki Sugiura et al.: "Cannabinoid receptors and their endogenous ligands."J.Biochem.. 132. 7-12 (2002)

Takayuki Sugiura 等人：“大麻素受体及其内源性配体。”J.Biochem.. 132. 7-12 (2002)

Sugiura, T. et al.: "Cannabinoid receptors and their endogenous ligands"J. Biochem. 132. 7-12 (2002)

Sugiura, T. 等人：“大麻素受体及其内源性配体”J.

Kishimoto, S. et al.: "2-Arachidonoylglycerol Induces the Migration of HL-60 Cells Differentiated into Macrophage-like Cells and Human Peripheral Blood Monocytes thuough the Cannabinoid CB2 Receptor-dependent Mechanism"J. Biol. Chem.. 278. 24469-24475 (20

Kishimoto, S. 等人：“2-花生四烯酰甘油通过大麻素 CB2 受体依赖性机制诱导分化为巨噬细胞样细胞和人外周血单核细胞的 HL-60 细胞迁移”J.

Takayuki Sugiura et al.: "Arachidonate Remodeling and Inflammation"Birkhauser Verlag Basal. 243 (2003)

Takayuki Sugiura 等人：“花生四烯酸重塑和炎症”Birkhauser Verlag Basal。