title: Specific PGF(2alpha) receptor (FP) antagonism and human uterine contractility in vitro.
abstract: OBJECTIVE
  PGF(2alpha) acts through its receptor, FP, as an important smooth muscle contractile agent. The aim of this study was to investigate the effects of specific FP antagonism, using the novel-specific FP non-competitive antagonist THG113.31, on spontaneous and agonist-elicited contractions in pregnant and non-pregnant human myometrium in vitro.
  
  
  METHODS
  Scientific study.
  
  
  METHODS
  University hospital and laboratories. Population Women undergoing caesarean section or hysterectomy.
  
  
  METHODS
  Biopsies of human myometrium were obtained at elective caesarean section (n= 22) and from hysterectomy specimens from premenopausal women (n= 8). Dissected strips were mounted in tissue baths under physiological conditions. The effects of THG113.31 on spontaneous and oxytocin-induced contractions, in pregnant myometrium, and on phenylephrine-induced contractions, in non-pregnant myometrium, were measured. The effects of PGF(2alpha) on spontaneous contractions, in pregnant tissue, in the presence and absence of THG113.31, were investigated. The integrals of contractile activity measured were compared with those from simultaneously run control experiments. The pD(2) and mean maximal effect observed for THG113.31, and for PGF(2alpha) in the presence and absence of THG113.31, were calculated.
  
  
  METHODS
  Changes in contractility.
  
  
  RESULTS
  THG113.31 exerted a potent relaxant effect in both spontaneous and oxytocin-induced contractility in pregnant tissue (P < 0.001), and phenylephrine-induced contractility in non-pregnant tissue (P < 0.001), compared with control experiments. PGF(2alpha) exerted a significant contractile effect on spontaneous contractions in pregnant tissue and this effect was not significantly attenuated by THG113.31 (P > 0.05).
  
  
  CONCLUSIONS
  THG113.31 exerted a significant relaxant effect on human spontaneous and oxytocin-induced contractility but did not alter PGF(2alpha)-elicited contractility. These data raise questions about the exact mechanism of effect of THG113.31 and its interaction with FP. The uterorelaxant potency of THG113.31 in human myometrium in vitro indicates that it may be of limited use as a tocolytic compound.
authors.affiliation: Department of Obstetrics and Gynaecology, Clinical Science Institute, University College Hospital Galway, Newcastle Road, Galway, Ireland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Friel
authors.forename: Michael W
authors.initials: MW
authors.lastname: O'Reilly
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Sexton
authors.forename: John J
authors.initials: JJ
authors.lastname: Morrison
mesh_terms: D000328:Adult; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007044:Hysterectomy; D066298:In Vitro Techniques; D008875:Middle Aged; D010121:Oxytocin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011247:Pregnancy; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D010656:Phenylephrine; D010121:Oxytocin