A role for phosphoinositide hydrolysis in human uterine smooth muscle during parturition

Abstract

Phosphoinositide hydrolysis is thought to be important in regulating a variety of intracellular signals, including Ca++ and prostaglandins, both of which have been implicated in the action of oxytocin during uterine smooth muscle contraction. We investigated the in vitro effect of oxytocin and various other uterotonic agents on phosphoinositide hydrolysis in gestational myometrium by measuring the production of inositol phosphates in tissue explants prelabeled with 3H-inositol. Oxytocin caused significant increases in all three inositol phosphates in myometrium at 3 minutes. Stimulation of inositol monophosphate production was sustained for 30 minutes and was dose dependent, with a half-maximal effect around 2 X 10(-8) mol/L. Platelet activating factor and alpha-adrenergic agonists also stimulated myometrial phosphoinositide hydrolysis, but carbachol prostaglandins E2 and F2 alpha had no effect. Vasopressin had greater efficacy than oxytocin for stimulating hydrolysis in gestational myometrium. Furthermore, in contrast to vasopressin, oxytocin had no effect on inositol phosphate production in nongestational myometrium. Oxytocin also stimulated arachidonic acid release and prostaglandin E2 and F2 alpha production in gestational myometrium. The hydrolysis of phosphatidylinositol by myometrium homogenates showed a precursor-product relationship for the production of diacylglycerol, monoacylglycerol, and arachidonic acid, indicative of a sequential action of phospholipase C and diacylglycerol lipase. These data demonstrate the potential for certain uterotonic agonists to use inositol lipid signaling to mobilize free arachidonic acid for prostaglandin production and to release intracellular Ca++ during excitation-contraction coupling.