{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T15:35:43Z","timestamp":1772897743420,"version":"3.50.1"},"reference-count":33,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[1999,3,1]]},"abstract":"<jats:p>Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We studied the effects of the type 3-selective phosphodiesterase inhibitor siguazodan, the type 4-selective phosphodiesterase inhibitor rolipram, and the nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) on proliferation of cultured HASM cells. At concentrations selective for the type 3 phosphodiesterase isoform, siguazodan inhibited both [<jats:sup>3<\/jats:sup>H]thymidine incorporation (IC<jats:sub>50<\/jats:sub>2 \u03bcM) and the increase in cell number (10 \u03bcM; 64% reduction) induced by platelet-derived growth factor-BB (20 ng\/ml). These effects were mimicked by IBMX. At concentrations selective for type 4 phosphodiesterase inhibition, rolipram was without effect. A 20-min exposure to siguazodan and rolipram did not increase whole cell cAMP levels. However, in HASM cells transfected with a cAMP-responsive luciferase reporter (p6CRE\/Luc), increases in cAMP-driven luciferase expression were seen with siguazodan (3.9-fold) and IBMX (16.5-fold). These data suggest that inhibition of the type 3 phosphodiesterase isoform present in airway smooth muscle results in inhibition of mitogenic signaling, possibly through an increase in cAMP-driven gene expression.<\/jats:p>","DOI":"10.1152\/ajplung.1999.276.3.l412","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T22:43:00Z","timestamp":1514068980000},"page":"L412-L419","source":"Crossref","is-referenced-by-count":9,"title":["Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition"],"prefix":"10.1152","volume":"276","author":[{"given":"Charlotte K.","family":"Billington","sequence":"first","affiliation":[{"name":"Division of Therapeutics, University Hospital, Nottingham NG7 2UH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil K.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Division of Therapeutics, University Hospital, Nottingham NG7 2UH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Swan","sequence":"additional","affiliation":[{"name":"Division of Therapeutics, University Hospital, Nottingham NG7 2UH, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark G. 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