Spontaneous contractions of myometrium from humans, non-human primate and rodents are sensitive to selective oxytocin receptor antagonism in vitro.
OBJECTIVE
To determine whether: 1. oxytocin receptor antagonists influence spontaneous contractions of myometrium from humans, non-human primates and rodents (in vitro), and 2. vasopressin V1a receptor antagonism is important for inhibition of spontaneous contractions in human myometrium.


METHODS
In vitro pharmacology of spontaneous contractions of myometrium from humans and animals.


METHODS
The research laboratories of a university department of obstetrics and gynaecology and a pharmaceutical industry research centre.


METHODS
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 V1a receptor antagonist (atosiban) were obtained. The effect of L-371,257 was also determined in myometrium from non-pregnant rats and marmosets.


METHODS
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.
Wilson
R J
RJ
Receptor Pharmacology Unit, GlaxoSmithKline Medicines Research Centre, Stevenage, UK.
Allen
M J
MJ
Nandi
M
M
Giles
H
H
Thornton
S
S
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D048588:Benzoxazines; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D009215:Myometrium / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011247:Pregnancy; D011323:Primates; D051381:Rats; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors*; D014590:Uterine Contraction / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D048588:Benzoxazines; D006727:Hormone Antagonists; C096766:L 371257; D010078:Oxazines; D010880:Piperidines; D018045:Receptors, Oxytocin; C047046:atosiban; D014668:Vasotocin