The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling

FEBS Letters

Avidor-Reiss, Tomer¹  Bayewitch, Michael¹  Vogel, Zvi¹  Barg, Jacob¹  Mechoulam, Raphael²  Levy, Rivka¹ 

[1] Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel;Department of Natural Products, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

关键词: Adenylate cyclase;    Anandamide;    Cannabinoid receptor;    δ 9-Tetrahydrocannabinol;    GTP-binding proteins;    Tricyclic cannabinoids;    AC;    adenylate cyclase;    CHO;    Chinese hamster ovary;    CTX;    cholera toxin;    δ 9-THC;    δ 9-tetrahydrocannabinol;    DMEM;    Dulbecco's modified Eagle's medium;    FAF-BSA;    fatty acid-free bovine serum albumin;    G proteins;    GTP proteins;    IBMX;    1-methyl-3-isobutylxanthine;    PMSF;    phenylmethylsulfonyl fluoride;    PTX;    pertussis toxin;   

DOI  :  10.1016/0014-5793(95)01207-U

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Two cannabinoid receptors, designated neuronal (or CB1) and peripheral (or CB2), have recently been cloned. Activation of CB1 receptors leads to inhibition of adenylate cyclase and N-type voltage-dependent Ca²⁺ channels. Here we show, using a CB2 transfected Chinese hamster ovary cell line, that this receptor binds a variety of tricyclic cannabinoid ligands as well as the endogenous ligand anandamide. Activation of the CB2 receptor by various tricyclic cannabinoids inhibits adenylate cyclase activity and this inhibition is pertussis toxin sensitive indicating that this receptor is coupled to the G_i/G₀ GTP-binding proteins. Interestingly, contrary to results with CB1, anandamide did not inhibit the CB2 coupled adenylate cyclase activity and δ ⁹-tetrahydrocannabinol had only marginal effects. These results characterize the CB2 receptor as a functional and distinctive member of the cannabinoid receptor family.

【 授权许可】

Unknown