{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T03:39:57Z","timestamp":1770349197360,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T00:00:00Z","timestamp":1193184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A major mechanism for Na<jats:sup>+<\/jats:sup> transport across epithelia occurs through epithelial Na<jats:sup>+<\/jats:sup> channels (ENaC). ENaC is a multimeric channel consisting of three subunits (\u03b1, \u03b2, and \u03b3). The \u03b1\u2010subunit is critical for ENaC function. In specific culture conditions, the rat submandibular gland epithelial cell line (SMG\u2010C6) demonstrates minimal Na<jats:sup>+<\/jats:sup> transport properties and exposure to dibutyryl cAMP (DbcAMP) for up to 48 h caused an elevation of \u03b1\u2010ENaC mRNA and protein expression and amiloride\u2010sensitive short\u2010circuit current (I<jats:sub>SC<\/jats:sub>). Here we examined the early signaling pathways evoked by DbcAMP which contribute to the eventual increase in Na<jats:sup>+<\/jats:sup> transport is present. Treatment with either of the protein kinase A (PKA) inhibitors KT5720 or H\u201089 followed by exposure to 1 mM DbcAMP for 24 h markedly attenuated DbcAMP\u2010induced \u03b1\u2010ENaC protein formation and I<jats:sub>SC<\/jats:sub>. Exposure of SMG\u2010C6 cells to 1 mM DbcAMP induced a rapid, transient phosphorylation of the cAMP response element binding protein (CREB). This response was attenuated in the presence of either KT5720 or H\u201089. Dominant\u2010negative CREB decreased DbcAMP\u2010induced \u03b1\u2010ENaC expression. Suppression of the extracellular signal\u2010regulated protein kinase (ERK 1,2) with PD98059 or the p38 mitogen\u2010activated protein kinase (MAPK) pathway with SB203580 reduced DbcAMP\u2010induced \u03b1\u2010ENaC protein levels in SMG\u2010C6 cells. DbcAMP\u2010induced phosphorylation of CREB was markedly attenuated by PD98059 or SB203580. DbcAMP\u2010induced activation of the either the p38 or the ERK 1,2 MAPK pathways was abolished by either of the PKA inhibitors, H\u201089 or KT5720. Cross talk between these signaling pathways induced by DbcAMP via the activation of CREB appears to contribute to increased levels of \u03b1\u2010ENaC observed after 24 h of treatment in SMG\u2010C6 epithelial cells. J. Cell. Physiol. 215: 101\u2013110, 2008. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21291","type":"journal-article","created":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T14:48:40Z","timestamp":1193237320000},"page":"101-110","source":"Crossref","is-referenced-by-count":25,"title":["Protein kinase A and mitogen\u2010activated protein kinase pathways mediate cAMP induction of \u03b1\u2010Epithelial Na<sup>+<\/sup> channels (\u03b1\u2010ENaC)"],"prefix":"10.1002","volume":"215","author":[{"given":"Shamimunisa B.","family":"Mustafa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Castro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison J.","family":"Falck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean 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