Abstract
Na+ reabsorption in the renal distal tubule is finely regulated by various factors such as aldosterone, vasopressin and extracellular osmolality to maintain body Na+ content and blood pressure. The amiloride-sensitive epithelial Na+ channel (ENaC) in the apical membrane contributes to transepithelial Na+ rebasorption as the rate limiting step in the distal nephron. Although we indicated that extracellular hypotonicity stimulates Na+ rebasorption through induction of ENaC gene expression, the mechanism behind this is still under investigation. We studied a physiological role of regulatory volume decrease (RVD) for sensing the extracellular hypotonicity in renal epithelial A6 cells. Extracellular hypotonicity induced the RVD-dependent tyrosine dephosphorylation of focal adhesion kinase (FAK) and paxillin by SRC homology 2 domain (SH2)-containing tyrosine phosphatase (SHP-2). This phenomenon was reproduced by decreasing cytosolic Cl- concentration ([Cl-]c) under an isotonic condition. These observations suggest that extracellular hypotonicity might be converted to the decrease in [Cl-]c through RVD which regulates the SHP-2-dependent FAK dephosphorylation, and indicate the importance of cytosolic Cl- in signal transduction for osmotic shock. Furthermore, hypotonicity caused the SHP-2-dependent stimulation of Na+ reabsorption through gene expression for adaptation to a new environment. Supported by JSPS 15659052 (YM), 15590189 (NN). [Jpn J Physiol 54 Suppl:S58 (2004)]
