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 ca uses increased arachidonic acid release and eicosanoid biosynthesis. H ere me demonstrate that the MAP kinase signal transduction pathway con tributes to this response, Treatment of WI-38 fibroblasts with anandam ide 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 p athway may therefore mediate the effects of anadamide on cPLA(2) activ ation and arachidonic acid release.