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Genomic and nongenomic dose-dependent biphasic effect of aldosterone on Na⁺/H⁺ exchanger in proximal S3 segment: role of cytosolic calcium

Department of Physiology and Biophysics, Instituto de Ciências Biomédicas, University of São Paulo, São Paulo, Brazil

Submitted 28 January 2008 ; accepted in final form 15 August 2008

The effects of aldosterone on the intracellular pH recovery rate (pHirr) via Na⁺/H⁺ exchanger and on the [Ca²⁺]_i were investigated in isolated rat S3 segment. Aldosterone [10^–12, 10^–10, or 10^–8 M with 1-h, 15- or 2-min preincubation (pi)] caused a dose-dependent increase in the pHirr, but aldosterone (10^–6 M with 1-h, 15- or 2-min pi) decreased it (these effects were prevented by HOE694 but not by S3226). After 1 min of aldosterone pi, there was a transient and dose-dependent increase of the [Ca²⁺]_i and after 6-min pi there was a new increase of [Ca²⁺]_i that persisted after 1 h. Spironolactone, actinomycin D, or cycloheximide did not affect the effects of aldosterone (15- or 2-min pi) but inhibited the effects of aldosterone (1-h pi) on pHirr and on [Ca²⁺]_i. RU 486 prevented the stimulatory effect of aldosterone (10^–12 M, 15- or 2-min pi) on both parameters and maintained the inhibitory effect of aldosterone (10^–6 M, 15- or 2-min pi) on the pHirr but reversed its stimulatory effect on the [Ca²⁺]_i to an inhibitory effect. The data indicate a genomic (1 h, via MR) and a nongenomic action (15 or 2 min, probably via GR) on [Ca²⁺]_i and on the basolateral NHE1 and are compatible with stimulation of the NHE1 by increases in [Ca²⁺]_i in the lower range (at 10^–12 M aldosterone) and inhibition by increases at high levels (at 10^–6 M aldosterone) or decreases in [Ca²⁺]_i (at 10^–6 M aldosterone plus RU 486).

mineralocorticoid stimulatory/inhibitory action; NHE1; proximal tubule; intracellular pH; intracellular Ca²⁺

This article has been cited by other articles:

				P. S. Pergher, D. Leite-Dellova, and M. de Mello-Aires Direct action of aldosterone on bicarbonate reabsorption in in vivo cortical proximal tubule Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1185 - F1193. [Abstract] [Full Text] [PDF]