title: G protein-coupled estrogen receptor 1-mediated effects in the rat myometrium.
abstract: G protein-coupled estrogen receptor 1 (GPER), also named GPR30, has been previously identified in the female reproductive system. In this study, GPER expression was found in the female rat myometrium by reverse transcriptase-polymerase chain reaction and immunocytochemistry. Using GPER-selective ligands, we assessed the effects of the GPER activation on resting membrane potential and cytosolic Ca(2+) concentration ([Ca(2+)](i)) in rat myometrial cells, as well as on contractility of rat uterine strips. G-1, a specific GPER agonist, induced a concentration-dependent depolarization and increase in [Ca(2+)](i) in myometrial cells. The depolarization was abolished in Na(+)-free saline. G-1-induced [Ca(2+)](i) increase was markedly decreased by nifedipine, a L-type Ca(2+) channel blocker, by Ca(2+)-free or Na(+)-free saline. Intracellular administration of G-1 produced a faster and transitory increase in [Ca(2+)](i), with a higher amplitude than that induced by extracellular application, supporting an intracellular localization of the functional GPER in myometrial cells. Depletion of internal Ca(2+) stores with thapsigargin produced a robust store-activated Ca(2+) entry; the Ca(2+) response to G-1 was similar to the constitutive Ca(2+) entry and did not seem to involve store-operated Ca(2+) entry. In rat uterine strips, administration of G-1 increased the frequency and amplitude of contractions and the area under the contractility curve. The effects of G-1 on membrane potential, [Ca(2+)](i), and uterine contractility were prevented by pretreatment with G-15, a GPER antagonist, further supporting the involvement of GPER in these responses. Taken together, our results indicate that GPER is expressed and functional in rat myometrium. GPER activation produces depolarization, elevates [Ca(2+)](i) and increases contractility in myometrial cells.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Tica
authors.forename: Erica C
authors.initials: EC
authors.lastname: Dun
authors.forename: Oana S
authors.initials: OS
authors.lastname: Tica
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Arterburn
authors.forename: G Cristina
authors.initials: GC
authors.lastname: Brailoiu
authors.forename: Tudor I
authors.initials: TI
authors.lastname: Oprea
authors.forename: Eugen
authors.initials: E
authors.lastname: Brailoiu
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D009215:Myometrium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects / Q000378:metabolism
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; C568862:4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline; D052117:Benzodioxoles; D002121:Calcium Channel Blockers; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; C520305:Gper1 protein, rat; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; D019284:Thapsigargin; D009543:Nifedipine; D002118:Calcium