Effects of anandamide on cannabinoid receptors in rat brain membranes.
Effects of anandamide on cannabinoid receptors in rat brain membranes.
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DOI：
10.1016/0006-2952(94)90134-1
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发表时间：
1994-02
影响因子：
5.8
通讯作者：
S. Childers;T. Sexton;Mary Beth Roy
中科院分区：
文献类型：
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作者：
S. Childers;T. Sexton;Mary Beth Roy
Anandamide（花生四烯乙醇酰胺）是最近从猪脑中分离出来的一种化合物，被认为是大麻素受体的内源性配体。本研究考察了大麻胺对大鼠脑膜中大麻素受体结合位点和腺苷酸环化酶的影响。在25°、90 min的条件下进行受体结合实验，anandamide （10 μM）对[3H]WIN 55212-2在小脑膜上的结合影响不大，明显导致了anandamide的降解。添加一般丝氨酸蛋白酶抑制剂苯基甲基磺酰氟（PMSF）可以防止这种降解，导致anandamide与[4H]WIN 55212-2结合的anic50值为90 nM。Anandamide对小脑膜腺苷酸环化酶具有gtp依赖的抑制作用，最大抑制水平略低于WIN 55212-2和CP-55,940， anic50值为1.9 μM。阿南丁胺对腺苷酸环化酶的影响具有区域特异性，抑制作用最大的部位是小脑和纹状体。这些结果表明，anandamide作用于大脑中g蛋白偶联的大麻素受体，其性质与外源性大麻素相似。
Anandamide (arachidonylethanolamide) is a compound recently isolated from porcine brain as a putative endogenous ligand at cannabinoid receptors. The present studies examined the effects of anandamide on cannabinoid receptor binding sites and adenylyl cyclase in rat brain membranes. Receptor binding experiments, conducted at 25° for 90 min, apparently resulted in significant degradation of anandamide, since anandamide (10 μM) had little effect on [3H]WIN 55212-2 binding in cerebellar membranes. Addition of the general serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) protected against this degradation, resulting in anic50value of 90 nM for anandamide versus [4H]WIN 55212-2 binding. Anandamide inhibited adenylyl cyclase in cerebellar membranes in a GTP-dependent manner, exhibiting a maximal inhibition level slightly less than that of WIN 55212-2 and CP-55,940, with anic50value of 1.9 μM. The effect of anandamide on adenylyl cyclase was region-specific, with maximal inhibition occurring in cerebellum and striatum. These results suggest that anandamide acts at G-protein-coupled cannabinoid receptors in brain with properties similar to those of exogenous cannabinoids.