Mechanism underlying endothelium-dependent relaxation by 2-methylthio-ADP in monkey cerebral artery

We recently reported endothelium-dependent relaxation caused by nucleotides in the non-human primate cerebral artery. here,we investigated the endothelium-dependent,nitric oxide-and prostanoid-independent relaxation induced by 2-methylthio-adp (2mesadp) in monkeycerebral artery. mechanical responses of isolated monkey cerebral arteries to the agents were isometricallyrecorded. in endothelium-intact arterial strips treated with indomethacin plus ng-nitro-l-arginine and partially contracted with prostaglandin f2α,2mesadp (1 nm - 10 μm) induced concentration-dependent relaxation that was abolished by removal of endothelium but was not influenced by either carboxy ptio or 18α-glycyrrhetinic acid. the 2mesadp-induced relaxation was inhibited by mrs2179 and u73122. the relaxation was markedly suppressed by exposure of the strips to high k+ media,but was not affected by glibenclamide. combination of charybdotoxin plus apamin markedly suppressed the relaxation,whereas iberiotoxin partially attenuated it. relaxation induced by 2mesadp was inhibited by arachidonyl trifluoromethyl ketone,ketoconazole,and 14,15-epoxyeicosa-5(z)-enoic acid. the inhibitors that affected the 2mesadp-induced relaxationdid not influence relaxation caused by sodium nitroprusside or forskolin. these findings indicatethat 2mesadp elicits 'endothelium-derived hyperpolarizing factor (edhf)-type' relaxation via stimulation of endothelial p2y1 receptors in monkey cerebral artery. furthermore,phospholipase a2,cytochrome p450-derived epoxyeicosatrienoic acids and ca2+-activated k+ channels appear o be involved in the relaxation. © 2010 the japanese pharmacological society.