Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Arachidonic Acids / pharmacology
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Benzoxazines
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Calcium / metabolism*
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Cannabinoids / metabolism
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Dose-Response Relationship, Drug
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Drug Interactions
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Endocannabinoids
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Glioma
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Glycerides / chemistry
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Glycerides / pharmacology*
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Hybrid Cells
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Ligands
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Morpholines / pharmacology
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Naphthalenes / pharmacology
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Neuroblastoma
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Neurons / drug effects*
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Piperidines / pharmacology
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Platelet Activating Factor / pharmacology
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Polyunsaturated Alkamides
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Pyrazoles / pharmacology
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Receptors, Cannabinoid
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Receptors, Drug / agonists
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Receptors, Drug / antagonists & inhibitors
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Receptors, Drug / metabolism*
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Rimonabant
Substances
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Arachidonic Acids
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Benzoxazines
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Cannabinoids
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Endocannabinoids
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Glycerides
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Ligands
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Morpholines
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Naphthalenes
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Piperidines
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Platelet Activating Factor
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Polyunsaturated Alkamides
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Pyrazoles
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Receptors, Cannabinoid
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Receptors, Drug
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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glyceryl 2-arachidonate
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Rimonabant
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Calcium
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anandamide