Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 13 P263

SFEBES2007 Poster Presentations Reproduction (13 abstracts)

EP2-mediated reduction of oxytocin-induced activity in term pregnant human myometrium

Deborah Fischer 1 , Kay Marshall 1 , Nicola Duckworth 1 , Diane Farrar 2 , Peter O’Donovan 2 & David Woodward 3

1University of Bradford, Bradford, West Yorkshire, United Kingdom; 2Bradford Royal Infirmary, Bradford, West Yorkshire, United Kingdom; 3Allergan Inc., Irvine, California, United States.

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.

Article tools

My recent searches

No recent searches.