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 micrograms/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 micrograms/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.
Baum
M
M
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas.
Moe
O W
OW
Gentry
D L
DL
Alpern
R J
RJ
D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids; D007536:Isomerism; D007672:Kidney Cortex / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*
D005938:Glucocorticoids; D012333:RNA, Messenger; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D000616:Aminoglutethimide; D003907:Dexamethasone