EVIDENCE FOR THE PRESENCE OF AH 13205-SENSITIVE EP(2)-PROSTANOID RECEPTORS IN THE PREGNANT BABOON BUT NOT IN THE PREGNANT SHEEP MYOMETRIUM NEAR-TERM

OBJECTIVE: Our purposes were to assess the effects of prostaglandin (PG) E(2) and PGF(2 alpha) on myometrial contractility in pregnant sheep and baboons in an in vitro superfusion study, and to characterize further the PGE-sensitive (EP) receptor subtype involved in the myometrial response to PGE(2) by using the selective prostanoid EP(2) agonist AH 13205. METHODS: Strip preparations of uterine muscle from 15 sheep (107-145 days' gestational age) and ten baboons (158-185 days' gestation) were studied. Cumulative concentration-response curves (CRC) were constructed to oxytocin (4.2 pmol/L to 0.42 mu mol/L, PGE(2) (0.1 nmol/L to 1 mu mol/L), and PGF(2 alpha) (1 nmol/L to 100 mu mol/L), and 50% effective concentration (EC50) values (mean and 95% confidence interval) were calculated. We also tested the hypothesis that PGE(2)-induced myometrial relaxation in pregnant baboons could be mediated by EP(2)-prostanoid receptors. Myometrial strips were stimulated by oxytacin (0.42 nmol/L), and CRCs to the EP(2)-agonist AH 13205 (0.1 nmol/L to 10 mu mol/L) were constructed. RESULTS: Prostaglandin F-2 alpha stimulated myometrial activity in a concentration-related fashion in all preparations from both sheep and baboons. The EC50 in the sheep myometrium PGF(2 alpha) (52 nmol/L, 95% confidence interval [CI] 25-110) was significantly (P <.05) lower than that in baboon myometrium (183 nmol/L, 95% CI 93-355). Oxytocin stimulated myometrial activity in preparations of both sheep (EC50 = 0.29 nmol/L, 95% CI 0.11-0.71) and baboon (EC50 = 0.31 nmol/L, 95% CI 0.18-0.52). In contrast, responses to PGE(2) were species-related: PGE, caused concentration-related stimulation of myometrial activity in sheep tissue (EC50 = 3.2 nmol/L, 95% CI 2.0-5.0), but induced concentration-related inhibition of activity in baboon myometrium (50% inhibitory concentration [IC50] = 21 nmol/L, 95% CI 2.2-203). A concentration-related inhibitory response to AH 13205 (IC50 = 3.56 nmol/L, 95% CI 1.28-5.99) was obtained in the baboon. In contrast, AH 13205 failed to inhibit comparable myometrial strip preparations from pregnant sheep. CONCLUSIONS: The present studies suggest that both sheep and baboon myometrium contain prostanoid receptors that mediate stimulation. In addition, baboon myometrium, like that from the human, contains AH 13205-sensitive EP receptors (EP(2) receptors), which mediate inhibition. The pregnant baboon may therefore represent a suitable animal model for investigations into the use of EP(2) agonists for the prevention of premature labor in humans.