title: Effect of oxytocin receptor blockade on rat myometrial responsiveness to prostaglandin f(2)(alpha).
abstract: In the present study we have shown that the genetic expression of prostaglandin (PG)F(2alpha) receptor (R) and cyclooxygenase (COX)-2 increases in laboring rat myometrium. This finding was associated with a relatively weak contractile in vitro response (E:(max)) of isolated uterine strips when challenged with PGF(2alpha). Five days postpartum PGF(2alpha)-R mRNA values exceeded those during labor while COX-2 mRNA was reduced to preparturient values. Maximal contractility of isolated strips stimulated with PGF(2alpha) at this time was enhanced and E:C(50) decreased. Oxytocin treatment of estrogen-primed nonpregnant rats down-regulated uterine contractile responsiveness to PGF(2alpha), leaving mRNA values for this receptor unchanged, whereas oxytocin receptor blockade with atosiban (an oxytocin receptor antagonist) left E:(max) unaltered. In contrast, atosiban treatment of pregnant rats resulted in a 2.5-fold increase in E:(max) and a considerably reduced EC(50) during labor when compared to untreated delivering rats. The increased contractile ability was associated with a threefold increase in PGF(2alpha)-R mRNA production, indicating that the regulation by atosiban of the PGF(2alpha)-induced response is exerted at the genetic level. Based on the present data we suggest that 1) PGF(2alpha)-R stimulation may not primarily exert a contracting role in the normally delivering myometrium, and 2) the presence of the PGF(2alpha)-R system in rat myometrium may explain the apparent functional redundancy of the oxytocinergic system during the process of birth in animals lacking oxytocin or where the oxytocin receptor is blocked. In this context PGF(2alpha) receptor stimulation may, in the absence of oxytocin receptor stimulation, exert the contractile forces needed for proper propulsion of the fetus.
authors.affiliation: Department of Internal Medicine and Endocrinology, Herlev Hospital, University of Copenhagen, Denmark. engstrom@mfi.ku.dk
authors.forename: T
authors.initials: T
authors.lastname: Engstrøm
authors.forename: P
authors.initials: P
authors.lastname: Bratholm
authors.forename: N J
authors.initials: NJ
authors.lastname: Christensen
authors.forename: H
authors.initials: H
authors.lastname: Vilhardt
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D009215:Myometrium / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015149:Tocolytic Agents / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D010120:Oxytocics; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; C047046:atosiban; D015237:Dinoprost; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D014668:Vasotocin