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

• Published in: American journal of physiology. Renal physiology 2008-11, Vol.295 (5), p.F1342-F1352
• Main Authors: Leite-Dellova, D C A, Oliveira-Souza, M, Malnic, G, Mello-Aires, M
• Format: Article
• Language: English
• Subjects: Aldosterone - pharmacology; Ammonium Chloride - pharmacology; Animals; Calcium; Calcium - metabolism; Calcium Signaling - physiology; Cycloheximide - pharmacology; Cytosol - metabolism; Dactinomycin - pharmacology; Gene Expression - drug effects; Genomics; Guanidines - pharmacology; Hormones; Hydrogen-Ion Concentration - drug effects; In Vitro Techniques; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Male; Methacrylates - pharmacology; Mifepristone - pharmacology; Rats; Rats, Wistar; Receptors, Glucocorticoid - genetics; Receptors, Mineralocorticoid - genetics; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Sodium - pharmacology; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Sodium-Hydrogen Exchangers - drug effects; Sodium-Hydrogen Exchangers - metabolism; Spironolactone - pharmacology; Sulfones - pharmacology
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00048.2008

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).