CHARACTERIZATION OF THE PROSTANOID RECEPTORS MEDIATING CONSTRICTION AND RELAXATION OF HUMAN ISOLATED UTERINE ARTERY

1 This study was undertaken to characterize pharmacologically the prostanoid receptor subtypes mediating constriction and relaxation of human isolated uterine artery. 2 U-46619 was a potent constrictor agonist on human uterine artery (EC(50) [95% CL]=3.5 [1.8-6.7] nM). Prostaglandin E(2) (PGE(2)), PGF(2), PGD(2) and PGI(2) only weakly constricted the uterine artery, being at least 100 times less potent than U-46619. The PGE(2) and PGI(2) constrictor effects may be modified by the potent dilator effects of these compounds. A number of agonists which show selectivity for FP-, DP- and EP-receptors including ICI 81008, BW 245C, sulprostone, rioprostil and butaprost, failed to cause any constriction at concentrations up to 30 mu M. 3 Constrictor responses induced by all agonists tested were reduced or abolished by the TP-receptor blocking drugs, GR 32191 and EP 092. pA(2) estimates for both antagonists versus U-46619 were 8.50, values which are consistent with their affinities at TP-receptors. 4 In preparations pre-constricted with phenylephrine (1 mu M) both PGI(2) and PGE(2) were potent relaxant agonists. The selective IP-receptor agonists, cicaprost and iloprost, also dilated human uterine artery and were approximately 10 fold more potent than PGI(2). The EP(2)-receptor agonists, butaprost and rioprostil and the selective DP-agonist, BW 245C, were at least 100 fold weaker than PGI(2) and PGE(2) suggesting that neither DP- nor EP(2) receptors were involved. 5 We conclude that TP-receptors mediate constriction, whereas IP- and possibly EP(4)-receptors mediate relaxation of human uterine artery.