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However, recently PGI<jats:sub>2<\/jats:sub>, acting <jats:italic>via<\/jats:italic> cAMP\/PKA, was found to increase contraction\u2010associated protein expression in myometrial cells and to promote oxytocin\u2010driven myometrial contractility. Cyclo\u2010oxygenase\u20102 (COX\u20102) is the rate\u2010limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX\u20102 expression, synthesis and activity. Three cAMP agonists (8\u2010bromo\u2010cAMP, forskolin and rolipram) increased COX\u20102 mRNA expression and further studies confirmed that this was associated with COX\u20102 protein synthesis and activity (increased PGE<jats:sub>2<\/jats:sub> and PGI<jats:sub>2<\/jats:sub> in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP\u2010effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP\u2010effector PDZ\u2010GEF<jats:sub>1\u20102<\/jats:sub>, without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX\u20102 expression and that PGE<jats:sub>2<\/jats:sub> acts through EP\u20102 to activate MAPK and increase COX\u20102. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2011.01413.x","type":"journal-article","created":{"date-parts":[[2011,8,19]],"date-time":"2011-08-19T18:08:38Z","timestamp":1313777318000},"page":"1447-1460","source":"Crossref","is-referenced-by-count":24,"title":["Cyclic AMP increases COX\u20102 expression <i>via<\/i> mitogen\u2010activated kinase in human myometrial cells"],"prefix":"10.1111","volume":"16","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suren R.","family":"Sooranna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyu","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandeep","family":"Kandola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip R.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Grammatopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,6,28]]},"reference":[{"key":"e_1_2_9_2_2","unstructured":"MacDormanMF MathewsTJ.Behind international rankings of infant mortality: how the United States compares with Europe. 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