PROSTANOID-INDUCED CONTRACTIONS ARE BLOCKED BY SULFONYLUREAS

The sulfonylureas glibenclamide and tolbutamide are blockers of ATP-regulated K+ channels. The present study shows that these drugs also block 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 found in endothelium-denuded preparations. The blockade is specific for prostanoids since contractions with norepinephrine, phenylephrine, serotonin, endothelin-1 or K+ (120 mM) are not or much less affected. On the other hand, contraction induced by activation of G-proteins with aluminium tetrafluoride anion (AIF(4)(-)) is significantly blocked by the sulfonylureas. Also on rat carotid artery the contraction of prostaglandin F-2 alpha is importantly blocked by glibenclamide. It is concluded that the sulfonylureas glibenclamide and tolbutamide exert a specific inhibitory influence on prostanoid-induced contractions. This inhibition might be due to interference at the level of regulatory G-proteins, since the contractions induced by agonists that, like the prostanoids, activate phospholipase C (serotonin, phenylephrine, norepinephrine, endothelin) are not blocked.