THE PERIPHERAL CANNABINOID RECEPTOR - ADENYLATE-CYCLASE INHIBITION AND G-PROTEIN COUPLING

Two cannabinoid receptors, designated neuronal (or CB1) and peripheral (or CB2), have recently been cloned, Activation of CB1 receptors lead s 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 cannabinoi d 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 indi cating that this receptor is coupled to the G(i)/G(o) GTP-binding prot eins, Interestingly, contrary to results with CB1, anandamide did not inhibit the CB2 coupled adenylate cyclase activity and Delta(9)-tetrah ydrocannabinol had only marginal effects, These results characterize t he CB2 receptor as a functional and distinctive member of the cannabin oid receptor family.