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Measurements of short-circuit current ( I<jats:sub>sc<\/jats:sub>) demonstrated stimulation (7\u201324 h) by the glucocorticoids hydrocortisone (EC<jats:sub>50<\/jats:sub> 13 nM), corticosterone (33 nM), prednisolone (70 nM), and dexamethasone (13 nM) over physiologically and therapeutically relevant concentrations and its block by amiloride (IC<jats:sub>50<\/jats:sub> 470 nM) and benzamil (57 nM), inhibitors of the epithelial sodium channel (ENaC). I<jats:sub>sc<\/jats:sub> was also partially inhibited by basolateral ouabain and Ba<jats:sup>2+<\/jats:sup>, indicating the participation of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase and a K<jats:sup>+<\/jats:sup> channel in Na<jats:sup>+<\/jats:sup> transport. By contrast, aldosterone stimulated I<jats:sub>sc<\/jats:sub> only at unphysiologically high concentrations (EC<jats:sub>50<\/jats:sub> 102 nM). The action of all steroids was blocked by mifepristone (RU-486; K<jats:sub>d<\/jats:sub> \u223c0.3 nM) but not by spironolactone ( K<jats:sub>d<\/jats:sub> \u223c0.7 \u03bcM). Expression of mRNA for the \u03b1-, \u03b2-, and \u03b3-subunits of ENaC was demonstrated in the presence and absence of glucocorticoids. These findings are the first to identify SCCD in the vestibular labyrinth as a site of physiologically significant ENaC-mediated Na<jats:sup>+<\/jats:sup> absorption and osmotically coupled water flux. They further demonstrate regulation of Na<jats:sup>+<\/jats:sup> transport by natural and therapeutic glucocorticoids. The results provide for the first time an understanding of the therapeutic benefit of glucocorticoids in the treatment of Meniere's disease, a condition that is associated with increased luminal fluid volume. <\/jats:p>","DOI":"10.1152\/ajprenal.00387.2003","type":"journal-article","created":{"date-parts":[[2004,3,8]],"date-time":"2004-03-08T20:14:04Z","timestamp":1078776844000},"page":"F1127-F1135","source":"Crossref","is-referenced-by-count":56,"title":["Glucocorticoids stimulate cation absorption by semicircular canal duct epithelium via epithelial sodium channel"],"prefix":"10.1152","volume":"286","author":[{"given":"Satyanarayana R.","family":"Pondugula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D.","family":"Sanneman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philine","family":"Wangemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre G.","family":"Milhaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Marcus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.573"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1987.5.2.202"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-42-6-1041"},{"key":"R4","unstructured":"Bohn MC, McEwen B, Luine VN, and Black IB. 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