2-ARACHIDONOYLGLYCEROL, A PUTATIVE ENDOGENOUS CANNABINOID RECEPTOR-LIGAND, INDUCES RAPID, TRANSIENT ELEVATION OF INTRACELLULAR FREE CA2-15 CELLS( IN NEUROBLASTOMA X GLIOMA HYBRID NG108)

Low concentrations of 2-arachidonoylglycerol were found to induce rapi d, transient elevation of intracellular free Ca2+ in NG108-15 cells (E C(50) was 150 nM). Free arachidonic acid, 2-palmitoylglycerol, 2-oleoy lglycerol, 2-linoleoylglycerol and 2-docosahexaenoylglycerol were inac tive. Anandamide acted as a partial agonist. Importantly, desensitizat ion was observed upon sequential challenge with 2-arachidonoylglycerol . Furthermore, cross-desensitization was observed between 2-arachidono ylglycerol and WIN 55212-2, a cannabinoid receptor agonist. Pretreatme nt of the cells with SR141716A, a cannabinoid receptor antagonist, abo lished the activities of both 2-arachidonoylglycerol and WIN 55212-2. These results strongly suggest that 2-arachidonoylglycerol and WIN 552 12-2 bind to a common cannabinoid receptor to elicit cellular response s and that ?2-arachidonoylglycerol has some physiological role in nerv ous tissues. (C) 1996 Academic Press, Inc.