Spontaneous contractions of myometrium from humans, non-human primate and rodents are sensitive to selective oxytocin receptor antagonism in vitro

Abstract

Objectives To determine whether: 1. oxytocin receptor antagonists influence spontaneous contractions of myometrium from humans, non-human primates and rodents ( in vitro), and 2. vasopressin V 1a receptor antagonism is important for inhibition of spontaneous contractions in human myometrium. Design In vitro pharmacology of spontaneous contractions of myometrium from humans and animals. Setting The research laboratories of a university department of obstetrics and gynaecology and a pharmaceutical industry research centre. Interventions Samples of human myometrium were obtained at caesarean section. Tissue strips were suspended in organ baths for isometric force recording. Cumulative concentration effect curves to a selective oxytocin receptor antagonist (L-371,257) and a mixed oxytocin/vasopressin V 1a receptor antagonist (atosiban) were obtained. The effect of L-371,257 was also determined in myometrium from non-pregnant rats and marmosets. Main outcome measures The inhibition of spontaneous myometrial contractions in vitro. Results L-371,257 and atosiban significantly inhibited spontaneous activity of human myometrium in a concentration-related manner ( P<0.05), although the effect was more pronounced with L-371,257. Spontaneous contractions of myometrium from non-pregnant rats and marmosets were also inhibited by L-371,257 (atosiban was not tested). Conclusions Spontaneous contractions of myometrium from humans, marmosets and rats are, at least in part, dependent on oxytocin receptor activity, in vitro. L-371,257 and atosiban may be inverse agonists. Selective non-peptide oxytocin receptor antagonists may be effective tocolytics.