Pharmacological characterization in vitro of prostanoid receptors in the myometrium of nonpregnant ewes

Abstract

Prostanoid receptors regulating the contractility of strips of myometrium obtained from nonpregnant ewes during the breeding season were classified pharmacologically. Natural prostanoids, receptor-type selective synthetic analogues, and selective antagonists were used where available. The natural prostanoids PGD2, PGE2, and PGF2 alpha were equipotent in causing contractions (pD2 values of 6.9, 6.7, and 6.9, respectively) but were 100 times less potent than oxytocin (pD2 = 9.2). The synthetic prostanoids iloprost (pD2 = 8.3), GR63799x (pD2 = 7.0), cloprostenol (pD2 = 6.8), and U46619 (pD2 = 6.2) also caused contractions. The effects of iloprost, but not of GR63799x, were blocked by the selective EP1 antagonist AH 6809. This suggests the presence of both EP1 and EP3 receptors. The similar potencies of cloprostenol and PGF2 alpha suggest the presence of FP receptors. Although the potency of the TP agonist U46619 was relatively low, its effects were blocked by the selective TP antagonist L 670596 (pKB = 8.4), an observation consistent with the presence of TP receptors. Thus, all currently recognized excitatory prostanoid receptors (EP1, EP3, FP and TP) appeared to be present. Contractions induced by cloprostenol and KCl could be inhibited by the beta-adrenoceptor agonist isoprenaline (pD2 = 8.8 against cloprostenol) and the Ca(2+)-channel blocker, D600 (pD2 = 6.3 against cloprostenol), but a number of relaxant prostanoids, BW245c, ZK110841, AH13205 and cicaprost, could not produce inhibition. These results suggest that DP, EP2 and IP receptors do not regulate contractility under these conditions.

Fetal-to-Maternal Progression of Prostaglandin H2 Synthase-2 Expression in Ovine Intrauterine Tissues During the Course of Labor1

“…Previous researchers had inferred the presence of excitatory PG receptors (EP-1, EP-3, and FP) in myometrium from nonpregnant and pregnant sheep, through pharmacological characterization, but had not detected the presence of the EP-2 and EP-4 receptors [22,23]. Those studies focused only on samples of myometrium collected at term, whereas here we report the presence of PG receptor gene expression at term and with the onset of parturition in myometrium.…”

“…The presence of excitatory (EP-1, EP-3, FP) as well as of inhibitory (EP-2) receptors has been established in myometrium from nonpregnant and pregnant women at term [19][20][21]. Stimulatory but not inhibitory receptors have been detected in myometrium from nonpregnant and pregnant sheep [22,23]. Even though PGs have been well established as stimulators of myometrial contractility at term, there is no information concerning changes in PG receptor expression in intrauterine tissues from the time of uterine activation until delivery.…”

Effects of Gestational Age and Labor on Expression of Prostanoid Receptor Genes in Baboon Uterus1

“…However, there is no significant change in EP 2 receptor gene expression in ovine myometrium in pregnancy [14]. This species difference in genetic expression is paralleled by functional differences in response of myometrial strips because both human [11] and baboon myometrium [18] relax in response to EP 2 receptor agonists, whereas these drugs are without effect in ovine myometrium [18,19]. We have also demonstrated reduced EP 2 receptor gene expression in the baboon cervix and decidua in association with labor, which suggests that this receptor may have a key role in the control of parturition [20].…”

Participation of Prostaglandin E2 in Contractile Activity of Inflamed Porcine Uterus

“…It is known that PGE 2 may both stimulate or inhibit the contractile activity of the uterus depending on its concentration and the physiological stage of the uterus (Crankshaw and Gaspar 1995;Popat and Crankshaw 2001;Cao et al 2002). PGE 2 is also considered a potent vasodilator and relaxant acting on MYO and thus an important mediator of inflammation, and a factor contributing to the development of pathological process and its maintenance (Slama et al 1991;Slama et al 1994).…”