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

被引:55
作者
BAXTER, GS
CLAYTON, JK
COLEMAN, RA
MARSHALL, K
SANGHA, R
SENIOR, J
机构
[1] UNIV BRADFORD,SCH PHARM,BRADFORD BD7 1DP,W YORKSHIRE,ENGLAND
[2] SMITHKLINE BEECHAM PHARMACEUT,NEUROL RES DEPT,HARLOW CM19 5AD,ESSEX,ENGLAND
[3] BRADFORD ROYAL INFIRM,BRADFORD BD9 6RJ,W YORKSHIRE,ENGLAND
[4] GLAXO RES & DEV LTD,WARE SG21 0DP,HERTS,ENGLAND
关键词
PROSTANOID RECEPTORS; HUMAN UTERINE ARTERY; TP-RECEPTORS AND CONSTRICTION; IP-RECEPTORS AND RELAXATION;
D O I
10.1111/j.1476-5381.1995.tb16393.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页码:1692 / 1696
页数:5
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