GLUCOCORTICOIDS REGULATE NHE-3 TRANSCRIPTION IN OKP CELLS

KP cells express NHE-3, an amiloride-resistant Na+/H+ antiporter, whic h is likely an isoform responsible for apical proton secretion by the proximal tubule. We have previously shown that an amiloride-resistant Na+/H+ antiporter in OKP cells is regulated by dexamethasone, a synthe tic glucocorticoid. The purpose of the present study was to examine th e mechanism for the glucocorticoid-mediated increase in Na+/H+ antipor ter activity. Incubation of OKP cells with 10(-6) M dexamethasone resu lted in a two- to threefold increase in NHE-3 mRNA abundance. This inc rease was seen after 4 h of incubation with dexamethasone, a time cour se similar to that found for Na+/H+ antiporter activity. To examine th e mechanism for the increase in NHE-3 mRNA abundance, mRNA half-life a nd in vitro transcription experiments were performed. NHE-3 mRNA had a half-life of 8 h in control and dexamethasone-treated cells. The rate of in vitro transcription was 1.8-fold greater when OKP cells were tr eated with dexamethasone. These data suggest that the glucocorticoid-m ediated increase in Na+/H+ antiporter activity is due to an increase i n NHE-3 gene transcription.