Glucocorticoids regulate Na+/H+ exchange expression and activity in region- and tissue-specific manner.

Na+/H+ exchangers (NHEs) are integral membrane proteins that exchange Na+ for H+ across membranes. Four isoforms have been cloned (NHE-1-4). NHE-3 localizes to the apical domain, and its expression is increased in dexamethasone-treated rats by Northern analysis. This stimulatory effect on expression is region and tissue specific, being present in ileum and proximal colon, but not in jejunum, distal colon, or kidney. The increase in transcript expression in ileum correlates with an increase in protein expression by immunoblotting. Changes in apical Na+/H+ exchange activity, as measured by 22Na uptake into brush-border membrane vesicles, correlate with expression differences, with significant increases observed in ileum and proximal colon. In situ hybridization showed NHE-3 mRNA only in villus and absorptive cells of control rats, the pattern not being altered by dexamethasone treatment. This suggests that dexamethasone does not increase expression by inducing crypt cells to express NHE-3 prematurely. We conclude that glucocorticoids selectively increase intestinal NHE-3 activity in a region-specific manner and that this effect also appears to be tissue specific.