2-Arachidonoylglycerol, a putative endogenous cannabinoid receptor ligand, induces rapid, transient elevation of intracellular free Ca2+ in neuroblastoma x glioma hybrid NG108-15 cells.
Low concentrations of 2-arachidonoylglycerol were found to induce rapid, transient elevation of intracellular free Ca2+ in NG108-15 cells (EC50 was 150 nM). Free arachidonic acid, 2-palmitoylglycerol, 2-oleoylglycerol, 2-linoleoylglycerol and 2-docosahexaenoylglycerol were inactive. Anandamide acted as a partial agonist. Importantly, desensitization was observed upon sequential challenge with 2-arachidonoylglycerol. Furthermore, cross-desensitization was observed between 2-arachidonoylglycerol and WIN 55212-2, a cannabinoid receptor agonist. Pretreatment of the cells with SR141716A, a cannabinoid receptor antagonist, abolished the activities of both 2-arachidonoylglycerol and WIN 55212-2. These results strongly suggest that 2-arachidonoylglycerol and WIN 55212-2 bind to a common cannabinoid receptor to elicit cellular responses and that 2-arachidonoylglycerol has some physiological role in nervous tissues.
Sugiura
T
T
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Kodaka
T
T
Kondo
S
S
Tonegawa
T
T
Nakane
S
S
Kishimoto
S
S
Yamashita
A
A
Waku
K
K
D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002118:Calcium / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D063388:Endocannabinoids; D005910:Glioma; D005989:Glycerides / Q000737:chemistry / Q000494:pharmacology*; D006822:Hybrid Cells; D008024:Ligands; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant
D001095:Arachidonic Acids; D048588:Benzoxazines; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D008024:Ligands; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D010972:Platelet Activating Factor; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094503:glyceryl 2-arachidonate; D000077285:Rimonabant; D002118:Calcium; C078814:anandamide