CALL FOR PAPERS Aldosterone and ENaC: From Genetics to Physiology Evidence for epidermal growth factor receptor as negative-feedback control in aldosterone-induced Na reabsorption

00378.2003.—Aldosterone enhances Na reabsorption via epithelial Na channels (ENaC). Aldosterone also stimulates the protein kinase ERK1/2- and the epidermal growth factor (EGF) receptor (EGFR)-signaling pathway. Yet EGF and ERK1/2 are known inhibitors of ENaC-mediated Na reabsorption. In the present study, using the well-established Madin-Darby canine kidney C7 cell line, we tested the hypothesis that EGFR represents a negative-feedback control for chronic aldosterone-induced Na reabsorption [amiloride-inhibitable short-circuit current (Isc)]. Mineralocorticoid receptor expression was confirmed by RT-PCR and Western blot analysis. Aldosterone en-hanced ERK1/2 phosphorylation in an EGFR-dependent way. Fur-thermore, aldosterone stimulated EGFR expression. Aldosterone (10 nmol/l) induced a small transient increase in Isc under control condi-tions. Inhibition of ERK1/2 phosphorylation with U-0126 (10 mol/l) stimulated Isc, indicating constitutive ENaC inhibition. Aldosteron