Effect of glucocorticoids on renal cortical NHE-3 and NHE-1 mRNA

Glucocorticoids play an important role in modulating proximal tubule acidification. Chronic systemic administration of dexamethasone increases the rate of bicarbonate absorption in isolated perfused proximal convoluted tubules and Na⁺/H⁺ antiporter activity in renal brush-border membrane vesicles. The proximal tubule expresses mRNA corresponding to two known Na⁺/H⁺ antiporter isoforms: NHE-3, an amiloride-resistant apical membrane Na⁺/H⁺ antiporter; and NHE-1, an amiloride-sensitive Na⁺/H⁺ antiporter found on most mammalian cells. Administration of dexamethasone for 1 and 2 days (600 μg/kg twice daily and 2 h before animals were killed) increased NHE-3 mRNA abundance 1.3- and 2.5-fold, respectively, but had no effect on NHE-1 mRNA abundance. Aminoglutethimide-induced glucocorticoid deficiency had no effect on NHE-1 or NHE-3 mRNA abundance. Incubation of proximal tubules for 3 h with 10^-5 M dexamethasone increased proximal tubule Na⁺/H⁺ antiporter activity from 0.69 ± 0.04 to 0.92 ± 0.03 pH units/min (P < 0.01); however, there was no increase in NHE-3 or NHE-1 mRNA abundance. Similarly, there was no effect on NHE-3 or NHE-1 mRNA abundance in rabbit renal cortex 4 h after intravenous administration of 600 μg/kg dexamethasone. Thus chronic dexamethasone increases NHE-3 but not NHE-1 mRNA abundance. The acute increase in Na⁺/H⁺ antiporter activity induced by dexamethasone occurs by mechanisms independent of changes in NHE-1 and NHE-3 mRNA abundance.