2-Arachidonoylglycerol, a candidate of endothelium-derived hyperpolarizingfactor

We investigated whether 2-arachidonoylglycerol, an endogenous cannabinoid r eceptor ligand, is involved in acetylcholine- and calcium ionaphore A23187- induced relaxations in the presence of NG-nitro-L-arginine methyl ester (L- NAME and indomethacin, which is considered to be mediated by endothelium-de rived hyperpolarizing factor (EDHF). In rabbit mesenteric arterial rings pr e-constricted with noradrenaline, 2-arachidonoylglycerol caused concentrati on-dependent relaxation. The 2-arachidonoylglycerol-induced relaxations wer e not affected by endothelium removal. N-piperidino-5 -(4-chlorophenyl)-1-( 2,4-dichlorophenyl)-4-methyl-3 pyrazole-caroxamide (SR141716A) and 1-(2,4-d ichlorophenyl)-5-(4-iodophenyl)- 1 H-pyrazole-3 -carboxamide (AM281), canna binoid CB, receptor antagonists, significantly attenuated 2-arachidonoylgly cerol-induced relaxation and the acethylcholine-induced relaxation only sli ghtly, but not the calcium ionophore A23187-induced relaxation. On the othe r hand, charybdotoxin plus apamin, Kf channel blockers, significantly atten uated acetylcholine and calcium ionohore A23187-induced relaxations but not 2-arachidonoylglycerol-induced relaxations. These results suggest that 2-a rachidonoylglycerol can cause relaxations via cannabinoid CB, receptors, bu t is not involved in EDHF-mediated relaxations. (C) 2001 Elsevier Science B .V. AU rights reserved.