Effects of Prostanoids on the Rat’s Myometrium in Vitro during Pregnancy1

Abstract

The objectives of this study were to determine the effects of pregnancy in the rat on the contractile response of the myometrium in vitro to a number of prostanoids. Longitudinally and circularly oriented strips were studied separately. Responses to PG (prostaglandin)F2 alpha, PDG2, the PGI2-mimetic iloprost, and the thromboxane (Tx) A2-mimetic U-46619 were investigated on Days 10, 15, 18, 20, 21, and 22 of pregnancy. Responses were prostanoid-dependent, and differences between longitudinal and circular strips were small. PGF2 alpha and PGD2 produced similar patterns, with a high potency but low maximal response on Day 10; thereafter potency fell to a minimum value on Day 18 and then gradually increased until Day 22, when it was still lower than at Day 10. In contrast, for PGE2 there were no changes in potency over the period of study (longitudinal muscle) or a slight increase between Days 15 and 21 (circular muscle). Both iloprost and U-46619 maintained a low potency throughout pregnancy. We conclude that the pregnant rat's myometrium is probably not a target for PGI2 or TxA2 and that the difference patterns of responses to PGE2 and PGF2 alpha during pregnancy support the hypotheses that these prostanoids act at different sites within the myometrium.

Prostaglandin F receptor expression in intrauterine tissues of pregnant rats

“…This pattern of FP receptor expression is similar to those previously reported for the myometrium [4,17] and entire uterus [2]. Responsiveness of the rat myometrium to PGF2α increases from Day 18 throughout the latter part of gestation [7]. Increases in FP receptor expression were reported to increase sensitivity of the myometrium to PGF2α action at term, even in the absence of increased PGF2α concentrations [4].…”

“…The PGs are recognized as the 'triggers' of labor [5] because the myometrium contracts in response to exogenous PGs both in vivo and in vitro [7,19], PG synthetic enzymes and levels in tissues and fluids increase before or at the time of labor, and inhibitors of PG synthesis delay birth and prolong pregnancy [15]. The current study clearly demonstrated that the FP receptor mRNA levels in rat uterus were low between Days 10 and 18 of gestation, significantly increased on Day 20, peaked during parturition, and fell rapidly after delivery.…”

The Initiation and Inhibition of Labor - Toward a Molecular Understanding

“…71 This evolution in the pattern of spontaneous con tractile activity with the initiation of labor is the manifestation of the transformation in the phenotype of the myometrium. With the approach of labor, the muscle demonstrates increased excitability (associated with a relative depolarization of the resting membrane potential, 67,72 it becomes highly respon sive to uterotonic agents 68,73,74 and the smooth muscle cells markedly increase their electrical coupling. 75 These changes act to increase the effectiveness of the uterotonic agents in generating high-frequency contractions and ensure that those contractions that are initiated rapidly spread to involve the entire uterus.…”

Changes in Expression of Contractile FP and Relaxatory EP2 Receptors in Pregnant Rat Myometrium during Late Gestation, at Labor, and Postpartum1

“…Each receptor was coupled to a specific intracellular signaling system by G proteins, and FP and EP receptors appear to mediate uterine contractions either with or without utilization of the phospholipase pathway [11]. After incubation of rat longitudinal and circular myometrial strips with various prostanoid receptor agonists and antagonists to induce or inhibit a contractile response, Crankshaw and Gaspar [12] concluded that rat myometrium was not a target for PGI 2 or Tx but yielded a different pattern of response for PGE 2 and PGF 2 , suggesting that these PGs act at different sites in the myometrium.…”