2-Arachidonoylglycerol, a candidate of endothelium-derived hyperpolarizing factor.
We investigated whether 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, is involved in acetylcholine- and calcium ionophore A23187-induced relaxations in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin, which is considered to be mediated by endothelium-derived hyperpolarizing factor (EDHF). In rabbit mesenteric arterial rings pre-constricted with noradrenaline, 2-arachidonoylglycerol caused concentration-dependent relaxation. The 2-arachidonoylglycerol-induced relaxations were not affected by endothelium removal. N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-caroxamide (SR141716A) and 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morholinyl-1H-pyrazole-3-carboxamide (AM281), cannabinoid CB(1) receptor antagonists, significantly attenuated 2-arachidonoylglycerol-induced relaxation and the acetylcholine-induced relaxation only slightly, but not the calcium ionophore A23187-induced relaxation. On the other hand, charybdotoxin plus apamin, K(+) channel blockers, significantly attenuated acetylcholine and calcium ionohore A23187-induced relaxations but not 2-arachidonoylglycerol-induced relaxations. These results suggest that 2-arachidonoylglycerol can cause relaxations via cannabinoid CB(1) receptors, but is not involved in EDHF-mediated relaxations.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan. skagota@mwu.mukogawa-u.ac.jp
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Kagota
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Yamaguchi
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Nakamura
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Sugiura
K
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Waku
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Kunitomo
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001685:Biological Factors / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology; D000077285:Rimonabant; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001095:Arachidonic Acids; D001685:Biological Factors; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D005989:Glycerides; D007476:Ionophores; D018377:Neurotransmitter Agents; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C067410:endothelium-dependent hyperpolarization factor; D000001:Calcimycin; C094503:glyceryl 2-arachidonate; D000077285:Rimonabant; C078814:anandamide