Endocrine Abstracts

Prostaglandin (PG) E₂ acts through its receptors (EP_1–4) to influence uterine contractility during gestation and parturition. The aim of the present study was to identify functional EP receptor targets in isolated myometrium from term pregnant, non-labouring donors by use of specific and novel EP agonists.

Biopsies of human myometrium were obtained at elective caesarean section from consenting term pregnant women, not in labour (38–40 weeks gestation; n=22). Myometrial strips were mounted longitudinally in immersion baths under physiological conditions and left to equilibrate for at least 90 minutes. Vehicle and concentration-effect curves (10⁻¹⁰ M to 10⁻⁵ M) for PGE₂, EP₂ agonists (butaprost, CP533536), EP₄ agonists (AGN201734, PDA124, AGN211330) and EP₁/EP₃ agonists (ONO-D1-004 and sulprostone) were added to individual organ baths and every 30-minute agonist or vehicle application was measured as area under the curve. Data were expressed as a percentage of the final contraction induced by hypotonic shock and analysed using two-way ANOVA with post-hoc Bonferroni’s test.

PGE₂ and AGN201734 exhibited biphasic responses in isolated myometrium, initially inhibiting spontaneous contractions compared to time-matched vehicles (P<0.05) with some excitation evoked at 10⁻⁵ M. EP₂ receptor agonists attenuated myogenic activity in a monophasic concentration-dependent manner (P<0.001), whilst the other EP₄ mimetics produced no response. Although sulprostone appeared to enhance the contractile frequency and amplitude, EP₁ and EP₃ agonists did not significantly alter myogenic responses to vehicle.

The predominant utero-relaxant effect of PGE₂ in isolated lower myometrium suggests that inhibitory receptors supersede contractile EP receptor function at term pregnancy. EP₂ agonists were most potent in mediating uterine quiescence; this indicates a crucial role for myometrial EP₂ receptors in pregnancy maintenance and parturition.