GLUCOCORTICOIDS STIMULATE NA+ H+ ANTIPORTER IN OKP CELLS

Previous studies have demonstrated that systemic administration of glu cocorticoids stimulates proximal tubule acidification in part by incre asing Na+/H+ antiporter activity; however, these studies could not exc lude the possibility that changes in Na+/H+ antiporter activity were s econdary to glucocorticoid-induced hemodynamic changes. The present st udy examined the effect of dexamethasone on Na+/H+ anti-porter activit y in quiescent OKP cells. Na+/H+ antiporter activity was assayed as th e initial rate of Na+-dependent pH recovery from an acid load. Intrace llular pH was measured using the pH-sensitive dye 2',7'-bis(carboxyeth yl)-5(6)-carboxyfluorescein (BCECF). Dexamethasone produced a dose- an d time-dependent stimulation of Na+/H+ antiporter activity in OKP cell s. Dexamethasone produced a 24% stimulation in Na+/H+ antiporter activ ity at 10(-9) M and an approximately 40% stimulation of Na+/H+ antipor ter activity at both 10(-8) and 10(-6) M. The effect of 10(-6) M dexam ethasone was seen within 4 h of incubation and was due to an increase in maximal velocity (V(max), 3.03 vs. 1.79 pH units/min) with no chang e in the affinity constant for sodium (K(Na), 47.2 vs. 42.0 mM). The s timulatory effect of dexamethasone on Na+/H+ antiporter activity was b locked by cycloheximide and was not observed with 10(-8) M aldosterone . These data demonstrate a direct effect of glucocorticoids to stimula te Na+/H+ antiporter activity in OKP cells.