Journal of Biological Chemistry
Volume 280, Issue 43, 28 October 2005, Pages 35807-35814
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Mechanisms of Signal Transduction
Rapid Effects of Dexamethasone on Intracellular pH and Na+/H+ Exchanger Activity in Human Bronchial Epithelial Cells*

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Glucocorticoids have been shown to produce rapid nongenomic responses in airway epithelia. By using an intracellular pH (pHi) spectrofluorescence imaging system and the NH4 Cl acid-loading technique, we have shown that the synthetic glucocorticoid,dexamethasone, accelerated intracellular pH recovery after an acid load in a human bronchial epithelial cell line (16HBE14o cells). Exposure to NH4Cl (20 mm) elicited an intracellular acidification, followed by a pHi recovery. Inhibition of the Na+/H+ exchanger decreased the steady-state pHi and antagonized the dexamethasone stimulation of pHi regulation. The rapid effect of dexamethasone on pHi was neither affected by the inhibitor of transcription, cycloheximide, nor by the classical glucocorticoid and mineralocorticoid receptors antagonists, RU486 and spironolactone, respectively. The dexamethasone effect on pHi regulation was reduced by inhibitors of adenylate cyclase, cAMP-dependent protein kinase and mitogenactivated protein kinase (ERK1/2). By using a PepTag assay system and Western blotting, we have shown that dexamethasone stimulated cAMP-dependent protein kinase and mitogen-activated protein kinase activities. Taken together our results provide evidence for the rapid stimulation of Na+/H+ exchange activity by glucocorticoids in bronchial epithelial cells via a nongenomic mechanism involving cAMP-dependent protein kinase and mitogen-activated protein kinase ERK1/2 pathways.

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This work was supported by INSERM, Vaincre la Mucoviscidose, the Regional Council of Languedoc-Roussillon (France), Wellcome Trust Grant 055695/Z/98/Z/CH/TG/JF, and the Higher Education Authority of Ireland PRTLI fund. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.