{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:48:58Z","timestamp":1782514138243,"version":"3.54.5"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Progesterone (P4) and cyclic adenosine monophosphate (cAMP) are regarded as pro\u2010quiescent factors that suppress uterine contractions during pregnancy. We previously used human primary cells in vitro and mice in vivo to demonstrate that simultaneously enhancing myometrial P4 and cAMP levels may reduce inflammation\u2010associated preterm labor. Here, we assessed whether aminophylline (Ami; phosphodiesterase inhibitor) and P4 can reduce myometrial contractility and contraction\u2010associated proteins (CAPs) better together than individually; both agents are clinically used drugs. Myometrial tissues from pregnant non\u2010laboring women were treated ex vivo with Ami acutely (while spontaneous contracting) or throughout 24\u2010h tissue culture (\u00b1P4); isometric tension measurements, PKA assays, and Western blotting were used to assess tissue contractility, cAMP action, and inflammation. Acute (1\u00a0h) treatment with 250 and 750\u00a0\u03bcM Ami reduced contractions by 50% and 84%, respectively, which was not associated with a directly proportional increase in whole tissue PKA activity. Sustained myometrial relaxation was observed during 24\u2010h tissue culture with 750\u00a0\u03bcM Ami, which did not require P4 nor reduce CAPs. COX\u20102 protein can be reduced by 300\u00a0nM P4 but this did not equate to myometrial relaxation. Ami (250\u00a0\u03bcM) and P4 (100 and 300\u00a0nM) co\u2010treatment did not prevent oxytocin\u2010augmented contractions nor reduce CAPs during interleukin\u20101\u03b2 stimulation. Overall, Ami and P4 co\u2010treatment did not suppress myometrial contractions more than either agent alone, which may be attributed to low specificity and efficacy of Ami; cAMP and P4 action at in utero neighboring reproductive tissues during pregnancy should also be considered.<\/jats:p>","DOI":"10.1002\/prp2.818","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T09:59:42Z","timestamp":1625479182000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluating aminophylline and progesterone combination treatment to modulate contractility and labor\u2010related proteins in pregnant human myometrial tissues"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4669-7029","authenticated-orcid":false,"given":"Pei F.","family":"Lai","sequence":"first","affiliation":[{"name":"Division of Reproductive and Developmental Biology Department of Metabolism, Digestion and Reproduction Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7239-9431","authenticated-orcid":false,"given":"Roger C.","family":"Young","sequence":"additional","affiliation":[{"name":"PreTeL, Inc. 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