THE MAP KINASE SIGNAL-TRANSDUCTION PATHWAY IS ACTIVATED BY THE ENDOGENOUS CANNABINOID ANANDAMIDE

Anandamide is an endogenous ligand for Delta(9)-tetrahydrocannabinol (THC) receptors, Incubation of cultured cells with anandamide or THC causes increased arachidonic acid release and eicosanoid biosynthesis. Here me demonstrate that the MAP kinase signal transduction pathway contributes to this response, Treatment of WI-38 fibroblasts with anandamide causes increased MAP kinase activity and increased pbosphorylation of the arachidonate-specific cytoplasmic phospholipase A(2) (cPLA(2)). Significantly, MAP kinase phosphorylates and activates cPLA(2) [Lin, et al., Cell,72 (1993) 269-278], The MAP kinase signal transduction pathway may therefore mediate the effects of anadamide on cPLA(2) activation and arachidonic acid release.