Abstract
In renal epithelial A6 cells, hypotonicity induces Na+ reabsorption by translocation of epithelial Na+ channel (ENaC) in a protein tyrosine kinase (PTK)-dependent manner. However, it is unknown what type of PTK is involved in hypotonic action. We hypothesized that receptor tyrosine kinases (RTKs) existing in cell membrane act on ENaC translocation by sensing the hypotonicity-induced change of cell volume. To clarify the hypothesis, we examined a role of epidermal growth factor receptor (EGFR), one of the RTKs, in hypotonicity-induced ENaC translocation. AG1478, an inhibitor of EGFR, blocked the stimulatory action of hypotonicity on ENaC activity that was measured as benzamil-sensitive short-circuit current and conductance 120 min after exposure to hypotonicity. Next, we investigated the influences of ERK1/2 and PI3-K, representing two main downstream signaling pathways of EGFR. PD98059, an inhibitor of ERK1/2, did not affect the hypotonicity action on ENaC. The hypotonicity action on ENaC was inhibited by LY294002, an inhibitor of PI3-K. These findings indicate that the signal of hypotonicity is converted into EGFR activation, which causes ENaC translocation through a PI3-K-dependent pathway. [Jpn J Physiol 55 Suppl:S84 (2005)]
