The Effects of Prostanoids on Estrogen-Dominated Rat Myometrial Longitudinal Muscle in Vitro1

Publisher Website
Google Scholar
Abstract
The purpose of these experiments was to characterize the contractile response of longitudinal muscle from the estrogen-dominated rat uterus to natural and synthetic prostanoids. The biological significance is 1) to provide evidence for or against a physiological role for each natural prostanoid in the regulation of myometrial activity, 2) to determine if each prostanoid has pharmacological potential for the manipulation of myometrial activity, and 3) to understand the structural requirements for prostanoid action on the myometrium. All analogs tested produced excitation of the myometrium in vitro through what appeared to be a direct action on the muscle. The order of potency of the natural prostanoids was prostaglandin (PG) F2.alpha. = PGD2 = PGE2 PGE1 > PGA2 = PGB2 = 6-keto-PGF1.alpha.. This order of potency was not consistent with any single currently recognized prostanoid receptor. Furthermore, PGF2.alpha. had an EC 50 (effective concentration that produces 50% of the maximal response) of 0.5 .mu.M, which was low in comparison to other PGF2.alpha.-sensitive tissues. There were large differences in the maximum tension developed in response to the prostanoids tested, only PGF2.alpha., PGE2 and 6-keto PGF1.alpha. were full agonists. Although the simplest explanation of these data was that the rat uterus contains a single novel type of prostanoid receptor, the existence of multiple receptor subtypes could not be disproved. Evidence from the effect of synthetic analogs suggested that neither thromboxane A2 nor PGI2 are physiological regulators of activity in this tissue.