Abstract
We have previously reported that hypotonic shock stimulates Na+ reabsorption by activating a PTK-dependent pathway and that hypotonic shock causes a decrease in cytosolic Cl- concentration ([Cl-]c) through regulatory volume decrease (RVD) in renal epithelial A6 cells. In this report, we found that hypotonic shock increased tyrosine phosphorylation of src kinase at pY416 (an active site of src kinase) in a manner dependent on the RVD-induced decrease in [Cl-]c. We further found that a decreasse in [Cl-]c caused a significant increase in tyrosine phosphorylation of src kinase at pY416 under an isotonic condition without any effect on tyrosine phosphorylation state of src kinase at pY527 (an inactive site of src kinase). Furthermore, pretreatment with PP2 (a specific inhibitor of src kinase) abolished the hypotonic shock-induced stimulation of Na+ rebasorption and alpha-subunit of epithelial Na+ channel (ENaC) mRNA expression. Taken together these results, it is suggested that hypotonic shock stimulates Na+ rebasorption through induction of alpha-ENaC gene expression by activating src kinase through the RVD-dependent decrease in [Cl-]c. Supported by Grants-in-Aids from JSPS (17590191 and 17390057). [J Physiol Sci. 2006;56 Suppl:S115]
