title: Spontaneous contractions of myometrium from humans, non-human primate and rodents are sensitive to selective oxytocin receptor antagonism in vitro.
abstract: 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.
authors.affiliation: Receptor Pharmacology Unit, GlaxoSmithKline Medicines Research Centre, Stevenage, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wilson
authors.forename: M J
authors.initials: MJ
authors.lastname: Allen
authors.forename: M
authors.initials: M
authors.lastname: Nandi
authors.forename: H
authors.initials: H
authors.lastname: Giles
authors.forename: S
authors.initials: S
authors.lastname: Thornton
mesh_terms: 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*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D048588:Benzoxazines; D006727:Hormone Antagonists; C096766:L 371257; D010078:Oxazines; D010880:Piperidines; D018045:Receptors, Oxytocin; C047046:atosiban; D014668:Vasotocin