Interspecies differences in thromboxane A receptors are distinguished by glibenclamide

Barbara K. Kemp, Grant A. McPherson

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3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalEuropean Journal of Pharmacology
Volume354
Issue number2-3
DOIs
Publication statusPublished - 7 Aug 1998

Keywords

  • Aorta
  • Coronary artery
  • GR32191
  • Mesenteric artery
  • Sulphonylurea
  • Thromboxane A
  • U46619

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