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Similar to OT, prostaglandins (PGs) play key roles in myometrial contractility and cervical ripening. Inhibition of PG synthesis\/activity is used to delay preterm birth. Thus, targeting the PG pathway in combination with an OTR-A may be an effective strategy for delaying preterm delivery. In this study, we examined the effects of atosiban and nolasiban on PGF<jats:sub>2\u03b1<\/jats:sub>-induced contractions and pro-inflammatory responses in human pregnant myometrium. Both OTR-As, atosiban and nolasiban, inhibited PGF<jats:sub>2\u03b1<\/jats:sub>-induced contractions in a dose-dependent manner (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 and<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, res<jats:italic>p<\/jats:italic>ectively). These inhibitory effects involved the suppression of PGF<jats:sub>2\u03b1<\/jats:sub>-mediated increase in intracellular calcium levels. In addition, the OTR-As significantly suppressed PGF<jats:sub>2\u03b1<\/jats:sub>-induced activation of pro-inflammatory pathways such as NF-\u03baB and mitogen activated protein kinases\u00a0(MAPKs), and the subsequent expression of contraction-associated-protein, COX-2. We have demonstrated that atosiban and nolasiban not only inhibit contractions elicited by OT, but also inhibit contractions and inflammation induced by PGF<jats:sub>2\u03b1<\/jats:sub>. This suggests a possible crosstalk between OTR and PG receptor signalling and highlights the importance of understanding G protein-coupled receptor interactions\/crosstalk in the development of future tocolytics.<\/jats:p>","DOI":"10.1038\/s41598-019-42181-2","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T10:04:10Z","timestamp":1554717850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Oxytocin Receptor Antagonists, Atosiban and Nolasiban, Inhibit Prostaglandin F2\u03b1-induced Contractions and Inflammatory Responses in Human Myometrium"],"prefix":"10.1038","volume":"9","author":[{"given":"Sung Hye","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Riaposova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauwa","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Pohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Chollet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Gotteland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4206-737X","authenticated-orcid":false,"given":"Aylin","family":"Hanyaloglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip R.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7579-4947","authenticated-orcid":false,"given":"Vasso","family":"Terzidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,8]]},"reference":[{"key":"42181_CR1","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1016\/S0140-6736(02)11476-0","volume":"360","author":"MM Slattery","year":"2002","unstructured":"Slattery, M. 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P.B. has worked as a consultant to Boehringer Ingelheim, GlaxoSmithKline, Merck Serono, ObsEva SA and Tokyo Tanabe Pharmaceuticals, drug companies with an interest in the pharmacological effects of oxytocin and oxytocin antagonists. P.B. holds shares of ObsEva SA. J.P.G. and O.P. are salaried employees of ObsEva SA. A.C. is a consultant to ObsEva SA.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"5792"}}