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 F2 alpha, prostaglandin E2 and the thromboxane A2 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 (AlF4-) is significantly blocked by the sulfonylureas. Also on rat carotid artery the contraction of prostaglandin F2 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.
Delaey
C
C
Department of Physiology and Physiopathology, University of Gent, Belgium.
Van de Voorde
J
J
D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D015221:Potassium Channels; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D013453:Sulfonylurea Compounds; D015237:Dinoprost