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 we 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 phosphorylation of the arachidonate-specific cytoplasmic phospholipase A2 (cPLA2). Significantly, MAP kinase phosphorylates and activates cPLA2 [Lin, et al., Cell, 72 (1993) 269-278]. The MAP kinase signal transduction pathway may therefore mediate the effects of anadamide on cPLA2 activation and arachidonic acid release.
Wartmann
M
M
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605.
Campbell
D
D
Subramanian
A
A
Burstein
S H
SH
Davis
R J
RJ
D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D063388:Endocannabinoids; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010766:Phosphorylation; D053284:Polyunsaturated Alkamides; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D016718:Arachidonic Acid; D011494:Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; C078814:anandamide