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This is a crucial regulatory mechanism for lung liquid clearance at birth and thereafter. This study investigated the influence of the gaseous signaling molecule hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) on \u03b2-adrenergic agonist-regulated pulmonary sodium and liquid absorption. Application of the H<jats:sub>2<\/jats:sub>S-liberating molecule Na<jats:sub>2<\/jats:sub>S (50 \u03bcM) to the alveolar compartment of rat lungs in situ decreased baseline liquid absorption and abrogated the stimulation of liquid absorption by the \u03b2-adrenergic agonist terbutaline. There was no additional effect of Na<jats:sub>2<\/jats:sub>S over that of the ENaC inhibitor amiloride. In electrophysiological Ussing chamber experiments with native lung epithelia ( Xenopus laevis), Na<jats:sub>2<\/jats:sub>S inhibited the stimulation of amiloride-sensitive current by terbutaline. \u03b2-adrenergic agonists generally increase ENaC abundance by cAMP formation and activation of PKA. Activation of this pathway by forskolin and 3-isobutyl-1-methylxanthine increased amiloride-sensitive currents in H441 pulmonary epithelial cells. This effect was inhibited by Na<jats:sub>2<\/jats:sub>S in a dose-dependent manner (5\u201350 \u03bcM). Na<jats:sub>2<\/jats:sub>S had no effect on cellular ATP concentration, cAMP formation, and activation of PKA. By contrast, Na<jats:sub>2<\/jats:sub>S prevented the cAMP-induced increase in ENaC activity in the apical membrane of H441 cells. H441 cells expressed the H<jats:sub>2<\/jats:sub>S-generating enzymes cystathionine-\u03b2-synthase, cystathionine-\u03b3-lyase, and 3-mercaptopyruvate sulfurtransferase, and they produced H<jats:sub>2<\/jats:sub>S amounts within the employed concentration range. These data demonstrate that H<jats:sub>2<\/jats:sub>S prevents the stimulation of ENaC by cAMP\/PKA and, thereby, inhibits the proabsorptive effect of \u03b2-adrenergic agonists on lung liquid clearance. <\/jats:p>","DOI":"10.1152\/ajpregu.00489.2014","type":"journal-article","created":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T06:53:30Z","timestamp":1422514410000},"page":"R636-R649","source":"Crossref","is-referenced-by-count":19,"title":["Hydrogen sulfide decreases \u03b2-adrenergic agonist-stimulated lung liquid clearance by inhibiting ENaC-mediated transepithelial sodium absorption"],"prefix":"10.1152","volume":"308","author":[{"given":"Alisa M.","family":"Agn\u00e9","sequence":"first","affiliation":[{"name":"Institute of Animal Physiology, Department of Molecular Cell Physiology, Justus-Liebig University, Giessen, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Peter","family":"Baldin","sequence":"additional","affiliation":[{"name":"Institute 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