Anandamide, an endogenous cannabinomimetic substance, modulates rat brain protein kinase C in vitro.
Anandamide (AnNH, N-arachidonoyl-ethanolamine) has been recently proposed as the endogenous ligand for mammalian brain cannabinoid receptor. Non-cannabinoid receptor-mediated, intracellular actions have been also found for this novel mediator. Here we present evidence for the modulation by anandamide of rat brain protein kinase C (PKC) activity in vitro. The ethanolamide of arachidonic acid (AA) was more active than the free acid in increasing phosphatidylserine (PS)-induced PKC activation (EC50 = 40 microM), but inhibited dioleylglycerol-induced potentiation of both Ca(2+)- and Ca2+/PS-induced PKC activation (IC50 = 8 microM and 30 microM, respectively). A dual modulatory action of anandamide on PKC, exerted by binding to the diacylglycerol regulatory site, is hypothesized in rat brain.
De Petrocellis
L
L
Istituto di Cibernetica, C.N.R., Naples, Italy.
Orlando
P
P
Di Marzo
V
V
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D001665:Binding Sites; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D063388:Endocannabinoids; D004789:Enzyme Activation; D007700:Kinetics; D010718:Phosphatidylserines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D010718:Phosphatidylserines; D053284:Polyunsaturated Alkamides; D016718:Arachidonic Acid; D011493:Protein Kinase C; D002118:Calcium; C078814:anandamide