{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:50:40Z","timestamp":1787784640305,"version":"build-2784847793"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nifedipine, an L\u2010type voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> channel (L\u2010VGCC) blocker, is one of the most used tocolytics to treat preterm labor. In clinical practice, nifedipine efficiently decreases uterine contractions, but its efficacy is limited over time, and repeated or maintained nifedipine\u2010based tocolysis appears to be ineffective in preventing preterm birth. We aimed to understand why nifedipine has short\u2010lasting efficiency for the inhibition of uterine contractions. We used ex vivo term pregnant human myometrial strips treated with cumulative doses of nifedipine. We observed that nifedipine inhibited spontaneous myometrial contractions in tissues with high and regular spontaneous contractions. By contrast, nifedipine appeared to increase contractions in tissues with low and\/or irregular spontaneous contractions. To investigate the molecular mechanisms activated by nifedipine in myometrial cells, we used the pregnant human myometrial cell line PHM1\u201041 that does not express L\u2010VGCC. The in vitro measurement of intracellular Ca<jats:sup>2+<\/jats:sup> showed that high doses of nifedipine induced an important intracellular Ca<jats:sup>2+<\/jats:sup> entry in myometrial cells. The inhibition or downregulation of the genes encoding for store\u2010operated Ca<jats:sup>2+<\/jats:sup> entry channels from the Orai and transient receptor potential\u2010canonical (TRPC) families in PHM1\u201041 cells highlighted the implication of TRPC1 in nifedipine\u2010induced Ca<jats:sup>2+<\/jats:sup> entry. In addition, the use of 2\u2010APB in combination with nifedipine on human myometrial strips tends to confirm that the pro\u2010contractile effect induced by nifedipine on myometrial tissues may involve the activation of TRPC channels.<\/jats:p>","DOI":"10.1002\/jcp.30666","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T04:59:19Z","timestamp":1641445159000},"page":"1980-1991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1"],"prefix":"10.1002","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5700-0883","authenticated-orcid":false,"given":"Lucile","family":"Yart","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Gynecology, and Obstetrics Geneva University Hospitals and University of Geneva Faculty of Medicine Geneva Switzerland"},{"name":"Translational Research Center in Oncohaematology University of Geneva Faculty of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Frieden","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism University of Geneva Faculty of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Konig","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism University of Geneva Faculty of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gynecology, and Obstetrics Geneva University Hospitals and University of Geneva Faculty of Medicine Geneva Switzerland"},{"name":"Translational Research Center in Oncohaematology University of Geneva Faculty of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Martinez de Tejada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gynecology, and Obstetrics Geneva University Hospitals and University of Geneva Faculty of Medicine Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2017.1331340"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009965"},{"issue":"2","key":"e_1_2_9_4_1","first-page":"70","article-title":"The physiological mechanism of uterine contraction with emphasis on calcium ion","volume":"1","author":"Alotaibi M. 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