Characterization of the prostanoid receptors mediating constriction and relaxation of human isolated uterine artery

Abstract

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 (EC50 [95% CL] = 3.5 [1.8-6.7] nM). Prostaglandin E2 (PGE2), PGF2 alpha, PGD2 and PGI2 only weakly constricted the uterine artery, being at least 100 times less potent than U-46619. The PGE2 and PGI2 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 microM. 3. Constrictor responses induced by all agonists tested were reduced or abolished by the TP-receptor blocking drugs, GR 32191 and EP 092. pA2 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 microM) both PGI2 and PGE2 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 PGI2. The EP2-receptor agonists, butaprost and rioprostil and the selective DP-agonist, BW 245C, were at least 100 fold weaker than PGI2 and PGE2 suggesting that neither DP- nor EP2 receptors were involved. 5. We conclude that TP-receptors mediate constriction, whereas IP- and possibly EP4-receptors mediate relaxation of human uterine artery.