Glucocorticoid activation of Na+/H+ exchange in renal brush border vesicles: kinetic effects

Abstract

Administration of the synthetic glucocorticoid dexamethasone to adrenalectomized rats increased Na+/H+ exchange activity in isolated renal brush border membrane vesicles. Treatment altered the initial rate of Na+ uptake by increasing Vmax (19.90 +/- 2.17 vs. 27.32 +/- 1.50 nmol.mg protein-1.5 s-1) and not the apparent affinity KNa+ (8.33 +/- 1.11 vs. 7.94 +/- 1.60 mM). Dexamethasone treatment resulted in a proportional increase in 1 mM Na+ uptake at every intravesicular pH measured. When these data were analyzed by the Hill equation, it was found that dexamethasone treatment did not change the apparent number of H+ binding sites (1.24 vs. 1.26) or the [H+]0.5 (0.33 vs. 0.32 microM) but increased the apparent Vmax (0.98 vs. 0.55 nmol.mg protein-1.2 s-1). It was also found that dexamethasone injections of 60 micrograms/100 g body wt resulted in maximum stimulation of exchange activity and that a significant increase in amiloride-sensitive Na+ uptake was detected within 12 h after a single dose of dexamethasone.

Glucocorticoids enhance acid activation of the Na+/H+ exchanger 3 (NHE3)

“…Glucocorticoids increase proximal tubule apical membrane Na/H antiporter activity in vivo and in cell culture (5,9,17). The present studies also demonstrate that glucocorticoids increase NHE3 protein abundance.…”

Glucocorticoids stimulate rabbit proximal convoluted tubule acidification.

“…In addition, glucocorticoids stimulate endogenous acid production which would result in greater acid excretion leading to a lower urine pH and bicarbonate concentration. Previous studies have examined the effect ofin vivo administration of glucocorticoids on renal Na +/ H + antiporter activity studied in vitro (10,11 ). Administration of the same dose of subcutaneous dexamethasone as in the present study resulted in a 70% increase in Na+/H+ antiporter activity ( 10).…”

“…Previous studies have demonstrated that systemic administration of dexamethasone increases Na+ / H + antiporter activity, whereas adrenalectomy did not produce a decrease in antiporter activity (8,10,11 ). This effect of dexamethasone is caused by an increase in the Vmax of the Na+/H+ antiporter, with no change in the Km for sodium ( 11 ).…”

Glucocorticoid Activation of Na+/H+Exchanger Isoform 3 Revisited

“…A similar mechanism appears to be responsible for renal proximal tubular sodium absorption, where administration of dexamethasone in rabbit for 1-2 days resulted in up to 2.5-fold increase in NHE3 transcript level, without an effect on NHE1 (10). As in ileum, glucocorticoids increased sodium absorption in renal brush border vesicles by increasing V max without altering the affinity for H ϩ or the Hill coefficient (36). Interestingly, incubation of isolated proximal tubules in dexamethasone for 3 h resulted in a 33% increase in NHE3 activity without a significant change in NHE3 or NHE1 transcript levels.…”