Interspecies differences in thromboxane A receptors are distinguished by glibenclamide

The ability of the thromboxane A₂ receptor antagonist, GR32191 ([1R-[1α(Z),2β3β,5α]]-7-[5-[[(1,1'-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-heptenoic acid), and the sulphonylurea, glibenclamide, to antagonise contractions t the trhomboxane A₂ mimetic, U46619 ((15S)-hydroxy-11α,9α(epoxymethano)prosta-5Z, 13E-dienoic acid), were assessed, in rat and guinea-pig isolated large (aorta) and small (mesentery and coronary) arteries. U46619 concentration-response curves were constructed in the absence and presence of GR32191 and glibenclamide and pK(B) values calculated. GR32191 caused significant rightward shifts in U46619 concentration-response curves and was a more potent antagonist in guinea-pig vessels (pK(B);9.4) than rat arteries (pK(B);7.9). Conversely, glibenclamide failed to inhibit contractions to U46619 in guinea-pig vessels but antagonised responses to U46619 in rat aorta (pK(B) = 6.1) and mesenteric artery (pK(B) = 6.3). In combination, GR32191 and glibenclamide caused a shift in the concentration-effect curve to U46619 in rat aorta that was additive. These results suggest that glibenclamide can discriminate between species differences in thromboxane A₂ receptors and may exert its inhibitory effect upon U46619-mediated contractions at the level of the thromboxane A₂ receptor. (C) 1998 Elsevier Science B.V. All rights reserved.