ANANDAMIDE, A BRAIN ENDOGENOUS COMPOUND, INTERACTS SPECIFICALLY WITH CANNABINOID RECEPTORS AND INHIBITS ADENYLATE-CYCLASE

A putative endogenous cannabinoid ligand, arachidonylethanolamide (ter med ''anandamide''), was isolated recently from porcine brain. Here we demonstrate that this compound is a specific cannabinoid agonist and exerts its action directly via the cannabinoid receptors. Anandamide s pecifically binds to membranes from cells transiently (COS) or stably (Chinese hamster ovary) transfected with an expression plasmid carryin g the cannabinoid receptor DNA but not to membranes from control nontr ansfected cells. Moreover, anandamide inhibited the forskolin-stimulat ed adenylate cyclase in the transfected cells and in cells that natura lly express cannabinoid receptors (N18TG2 neuroblastoma) but not in co ntrol nontransfected cells. As with exogenous cannabinoids, the inhibi tion by anandamide of the forskolin-stimulated adenylate cyclase was b locked by treatment with pertussis toxin. These data indicate that ana ndamide is an endogenous agonist that may serve as a genuine neurotran smitter for the cannabinoid receptor.