title: The effects of extracellular calcium-sensing receptor ligands on the contractility of pregnant human myometrium in vitro.
abstract: Ligands for extracellular calcium-sensing (CaS) receptors inhibit oxytocin-induced contractions of the rat's uterus. In this study, we investigated whether the CaS receptor ligands calindol, cinacalcet, and calhex 231 have similar effects on pregnant human myometrium. We compared their effects to those of the calcium-channel blocker nifedipine. In conventional concentration-effect experiments, both the mean contractile force (MCF) and the maximum amplitude of contractions induced by 1 nmol/L oxytocin were inhibited by nifedipine. Calindol and cinacalcet were ineffective as inhibitors, while calhex-231 produced partial inhibition. When single 10 μmol/L doses were applied calhex-231 produced a slowly developing inhibition, reducing the MCF to 38%, and amplitude to 34%, of vehicle controls after 1 hour. In similar experiments, calindol was ineffective while cinacalcet weakly inhibited only the amplitude. Immunohistochemistry revealed sparse expression of CaS receptors in pregnant human myometrium.
authors.affiliation: Department of Obstetrics and Gynaecology, National University of Ireland-Galway, Ireland. cranksha@mcmaster.ca
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Crankshaw
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Pistilli
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: O'Brien
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sweeney
authors.forename: Peter
authors.initials: P
authors.lastname: Dockery
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
authors.forename: John J
authors.initials: JJ
authors.lastname: Morrison
mesh_terms: D001549:Benzamides / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000069449:Cinacalcet; D003514:Cyclohexylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008024:Ligands; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D044169:Receptors, Calcium-Sensing / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: C506457:(R)-2-(1-(1-naphthyl)ethyl-aminom-ethyl)indole; D001549:Benzamides; C095550:CASR protein, human; D002121:Calcium Channel Blockers; D003514:Cyclohexylamines; D007211:Indoles; D008024:Ligands; C482333:N(1)-(4-chlorobenzoyl)-N(2)-(1-(1-naphthyl)ethyl)-1,2-diaminocyclohexane; D009281:Naphthalenes; D010120:Oxytocics; D044169:Receptors, Calcium-Sensing; D010121:Oxytocin; D009543:Nifedipine; D000069449:Cinacalcet
keywords: calcium-sensing receptors; calhex-231; calindol; cinacalcet; human myometrium; tocolysis