Endocrine Abstracts

Both prostaglandin (PG) E₂ and oxytocin are used clinically in the induction of labour. However, the functional co-expression of inhibitory PGE₂ receptors (EP₂) and contractile oxytocin receptors in lower segment myometrium is not fully understood. The aim of the present study was to elucidate EP₂ agonist effects on oxytocin-induced myogenic contractions and to identify their combined action on intracellular calcium (Ca²⁺) signalling mechanisms.

Myometrial biopsies were obtained from consenting women undergoing Caesarean section at term pregnancy not in labour (>37 weeks; n=17). Strips of myometrium were attached to isometric force transducers in physiological conditions and after development of regular myogenic activity, vehicle (saline) and concentration-effect curves for the EP₂ mimetic butaprost (10⁻¹⁰M to 10⁻⁵M), oxytocin (10⁻¹²M to 10⁻⁶M) and oxytocin in the presence of butaprost (10⁻⁶M) were measured. To perform Ca²⁺ assays, myometrial biopsies were dissociated for smooth muscle cell culture. Myocytes were incubated with the Ca²⁺ indicator fluo-4AM dye (2 μM) and washed. Treatments with oxytocin alone and with EP₂ agonists butaprost and CP533,536 (10⁻⁶M) were performed in triplicate using the FLIPR-Tetra. Results were expressed as means ±S.E. and analysed using 2-way ANOVA with Bonferroni’s post-hoc test.

Compared to the sustained vehicle myogenic activity, butaprost attenuated the amplitude of contractions in a concentration-dependent manner (P<0.001). Oxytocin augmented contractility was 4-fold greater than that seen with vehicle (P<0.001) with tetany exhibited above 10⁻⁹M. Potent responses to oxytocin were reduced in the presence of butaprost (P<0.05). Even so, pre-incubation of myocytes with EP₂ agonists had no influence on the concentration-dependent Ca²⁺ flux evoked by oxytocin.

The results of this study demonstrate a role for EP₂ agonists in attenuating oxytocin-mediated myometrial excitation. As EP₂ receptors represent novel tocolytic agents and do not appear to directly target Ca²⁺ transients, alternative signalling pathways for EP₂ agonists are currently being investigated.