title: A Role for Adrenergic Receptors in the Uterotonic Effects of Ergometrine in Isolated Human Term Nonlaboring Myometrium.
abstract: Ergometrine is a uterotonic agent that is recommended in the prevention and management of postpartum hemorrhage. Despite its long-standing use, the mechanism by which it acts in humans has never been elucidated fully. The objective of this study was to investigate the role of adrenoreceptors in ergometrine's mechanism of action in human myometrium. The study examined the hypothesis that α-adrenoreceptor antagonism would result in the reversal of the uterotonic effects of ergometrine.
  
  
  
  Myometrial samples were obtained from women undergoing elective cesarean delivery. The samples were then dissected into strips and mounted in organ bath chambers. After the generation of an ergometrine concentration-response curve (10 to 10 M), strips were treated with increasing concentrations of ergometrine (10 to 10 M) alone and ergometrine (10 to 10 M) in the presence of phentolamine (10 M), prazosin (10 M), propranolol (10 M), or yohimbine (10 M). The effects of adding ergometrine and the effect of drug combinations were analyzed using linear mixed effects models with measures of amplitude (g), frequency (contractions/10 min), and motility index (g×contractions/10 min).
  
  
  
  A total of 157 experiments were completed on samples obtained from 33 women. There was a significant increase in the motility index (adding 0.342 g × counts/10 min/μM; 95% confidence interval [CI], 0.253-0.431, P < .001), amplitude (0.078 g/μM; 95% CI, 0.0344-0.121, P = 5e-04), and frequency (0.051 counts/10 min/μM; 95% CI, 0.038-0.063, P < .001) in the presence of ergometrine. The α-adrenergic antagonist phentolamine and the more selective α1-adrenergic antagonist prazosin inhibited the ergometrine mediated increase in motility index, amplitude, and frequency (-1.63 g × counts/10 min/μM and -16.70 g × counts/10 min/μM for motility index, respectively).
  
  
  
  These results provide novel evidence for a role for α-adrenergic signaling mechanisms in the action of ergometrine on human myometrial smooth muscle in the in vitro setting. Information that sheds light on the mechanism of action of ergometrine may have implications for the development of further uterotonic agents.
authors.affiliation: From the *Department of Perioperative Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland; †UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; ‡Systems Biology Ireland, University College Dublin, Dublin, Ireland; and §UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Fanning
authors.forename: Florike
authors.initials: F
authors.lastname: Sheehan
authors.forename: Claire
authors.initials: C
authors.lastname: Leyden
authors.forename: Niamh
authors.initials: N
authors.lastname: Duffy
authors.forename: Luis F
authors.initials: LF
authors.lastname: Iglesias-Martinez
authors.forename: Michael F
authors.initials: MF
authors.lastname: Carey
authors.forename: Deirdre P
authors.initials: DP
authors.lastname: Campion
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Connor
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004874:Ergonovine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D011247:Pregnancy; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010120:Oxytocics; D011942:Receptors, Adrenergic, alpha; D004874:Ergonovine