thromboxane-a2 and tetraphenylphosphonium

The ability of a series of sulphonylurea derivatives to antagonise the vasorelaxant actions of the ATP-dependent K+ channel (K(ATP)) opener, levcromakalim, and the vasoconstrictor responses of the thromboxane A2 mimetic, U46619, were assessed in the pig coronary artery. The sulphonylurea derivatives of glibenclamide caused a rightward shift in the concentration-vasorelaxant response curve obtained to levcromakalim in arterial segments pre-constricted with acetylcholine (0.5 microM). From these shifts pK(B) were calculated to estimate the potency of these compounds as levcromakalim antagonists. Similarly U46619 concentration-vasoconstrictor responses curves were constructed in the absence and in the presence of a sulphonylurea derivative and pK(B) values calculated. Regression analysis of pK(B) values showed that there was a significant correlation between the potency of these compounds in the two systems studied indicating similar structure-activity relationships apply in both cases. That sulphonylureas regulate K(ATP) channel opening is well known and they do so through a specific receptor associated with the channel. The results obtained in this study may indicate that a sulphonylurea receptor may also be associated with thromboxane A2 excitation-contraction coupling.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Benzopyrans; Coronary Vessels; Cromakalim; Glyburide; Onium Compounds; Organophosphorus Compounds; Potassium Channels; Prostaglandin Endoperoxides, Synthetic; Pyrroles; Structure-Activity Relationship; Swine; Thromboxane A2; Vasoconstrictor Agents; Vasodilator Agents