PROSTANOID-INDUCED CONTRACTIONS ARE BLOCKED BY SULFONYLUREAS

The sulfonylureas glibenclamide and tolbutamide are blockers of ATP-re gulated K+ channels. The present study shows that these drugs also blo ck contractions induced by prostaglandin F-2 alpha, prostaglandin E(2) and the thromboxane A(2) mimetic U-46619 on rat aorta. This effect of sulfonylureas is not related to the endothelium since it is also foun d in endothelium-denuded preparations. The blockade is specific for pr ostanoids since contractions with norepinephrine, phenylephrine, serot onin, endothelin-1 or K+ (120 mM) are not or much less affected. On th e other hand, contraction induced by activation of G-proteins with alu minium tetrafluoride anion (AIF(4)(-)) is significantly blocked by the sulfonylureas. Also on rat carotid artery the contraction of prostagl andin F-2 alpha is importantly blocked by glibenclamide. It is conclud ed that the sulfonylureas glibenclamide and tolbutamide exert a specif ic inhibitory influence on prostanoid-induced contractions. This inhib ition might be due to interference at the level of regulatory G-protei ns, since the contractions induced by agonists that, like the prostano ids, activate phospholipase C (serotonin, phenylephrine, norepinephrin e, endothelin) are not blocked.