{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:16:04Z","timestamp":1790853364717,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2016,8,8]],"date-time":"2016-08-08T00:00:00Z","timestamp":1470614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"publisher","award":["208701"],"award-info":[{"award-number":["208701"]}],"id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Over 15 million babies are born prematurely each year with approximately 1 million of these babies dying as a direct result of preterm delivery.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>\u03b2<jats:sub>2<\/jats:sub>\u2010Adrenoreceptor agonists that act via cAMP can reduce uterine contractions to delay preterm labour, but their ability to repress uterine contractions lasts \u2264\u00a048\u00a0h and their use does not improve neonatal outcomes.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Previous research has suggested that cAMP inhibits myometrial contractions via protein kinase A (PKA) activation, but this has yet to be demonstrated with PKA\u2010specific agonists.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We investigated the role of PKA in mediating cAMP\u2010induced human myometrial relaxation, and the impact of prolonged cAMP elevation on myometrial contractility.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Our findings suggest that PKA is not the sole mediator of cAMP\u2010induced myometrial relaxation and that prolonged prophylactic elevation of cAMP alone is unlikely to prevent preterm labour (PTL).<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Acute cAMP elevation inhibits myometrial contractility, but the mechanisms responsible are not fully elucidated and the long\u2010term effects are uncertain. Both need to be defined in pregnant human myometrium before the therapeutic potential of cAMP\u2010elevating agents in the prevention of preterm labour can be realised. In the present study, we tested the hypotheses that PKA activity is necessary for cAMP\u2010induced myometrial relaxation, and that prolonged cAMP elevation can prevent myometrial contractions. Myometrial tissues obtained from term, pre\u2010labour elective Caesarean sections were exposed to receptor\u2010independent cAMP agonists to determine the relationship between myometrial contractility (spontaneous and oxytocin\u2010induced), PKA activity, HSP20 phosphorylation and expression of contraction\u2010associated and cAMP signalling proteins. Acute (1\u00a0h) application of cAMP agonists promoted myometrial relaxation, but this was weakly related to PKA activation. A PKA\u2010specific activator, 6\u2010Bnz\u2010cAMP, increased PKA activity (6.8\u00a0\u00b1\u00a02.0 mean fold<jats:italic>versus<\/jats:italic>vehicle;<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0313) without inducing myometrial relaxation. Spontaneous myometrial contractility declined after 24\u00a0h but was less marked when tissues were constantly exposed to cAMP agonists, especially for 8\u2010bromo\u2010cAMP (4.3\u00a0\u00b1\u00a01.2\u00a0mean fold<jats:italic>versus<\/jats:italic>vehicle;<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0043); this was associated with changes to calponin, cofilin and HSP20 phosphorylated\/total protein levels. Oxytocin\u2010induced contractions were unaffected by pre\u2010incubation with cAMP agonists despite treatments being able to enhance PKA activity and HSP20 phosphorylation. These data suggest that cAMP\u2010induced myometrial relaxation is not solely dependent on PKA activity and the ability of cAMP agonists to repress myometrial contractility is lost with prolonged exposure. We conclude that cAMP agonist treatment alone may not prevent preterm labour.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272320","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T20:22:15Z","timestamp":1466626935000},"page":"6369-6393","source":"Crossref","is-referenced-by-count":21,"title":["Differential impact of acute and prolonged cAMP agonist exposure on protein kinase A activation and human myometrium contractile activity"],"prefix":"10.1113","volume":"594","author":[{"given":"Pei F.","family":"Lai","sequence":"first","affiliation":[{"name":"Academic Department of Obstetrics &amp; Gynaecology Imperial College London London SW10 9NH UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Tribe","sequence":"additional","affiliation":[{"name":"Division of Women's Health Kings College London and Women's Health Academic Centre Kings Health Partners London SE1 7EH 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