The roles of prostaglandin EP 1 and 3 receptors in the control of human myometrial contractility

Abstract

Context: Prostaglandins are central to the processes of human labor. Prostaglandin E(2) (PGE(2)) synthesized within the uterus mediates cervical ripening and uterine contractions. PGE receptors, EP1 and EP3, may each mediate contractions, and represent potential therapeutic targets in the management of preterm labor. Studies of the expression and function of EP1 and EP3 in pregnant myometrium are inconsistent.

Objective: The objective of the study was to determine the relative importance of EP1 and EP3 in human myometrial contractility.

Design: We studied the expression of EP1 and EP3 in upper- and lower-segment myometrium at term in vivo and the effects of specific inhibitors on contractions in vitro.

Patients: Myometrial biopsies for both in vivo and in vitro studies were taken at cesarean section at term before or in labor in uncomplicated pregnancies.

Results: We found no differences in the expression of EP1 or EP3 at mRNA or protein level between the upper and lower segment myometrium and no overall changes associated with the onset of labor. Upon labor, EP1, but not EP3, was found to relocalize to the nucleus. In studies of contractility, we found no differences in spontaneous or PGE(2)-induced contractility between the upper- and lower-segment samples. Spontaneous contractions were inhibited by acetylsalicylic acid and were rescued by PGE(2). Although an EP1 antagonist, ZD6416, had no effect, an EP3 antagonist, L798106, inhibited both spontaneous and PGE(2)-induced contractions.

Conclusions: EP3 is the primary receptor subtype that mediates PGE(2) induced contractility in human pregnant myometrium at term and represents a possible therapeutic target.