Chronic metabolic acidosis increases nhe-3 protein abundance in rat
kidney.
Amb[umlaut]uhl, Patrice M., Morimasa Amemiya, Monika Danczkay, Marius
L[diaeresis]otscher, Brigitte Kaissling, Orson W. Moe, Patricia A.
Preisig, and Robert J. Alpern.
Department of Internal Medicine, University of Texas Southwestern
Medical Center, Dallas, Texas 75235-8856, Institute of Anatomy,
University of Z[umlaut]urich, CH-8057 Z[umlaut]urich, Switzerland,
Veterans Affairs Medical Center, Dallas, TX 75216
APStracts 3:0131F, 1996.
Chronic metabolic acidosis increases the activity of the proximal
tubule apical membrane Na/H antiporter, which is encoded
predominantly by the NHE-3 isoform. The present studies examined the
effect of chronic metabolic acidosis on apical membrane NHE-3 protein
abundance in rats. Rats subjected to NH4Cl in their drinking water
developed a metabolic acidosis which decreased in magnitude over 14
days. During this time, renal cortical brush border membrane NHE-3
protein abundance, assessed by western blot, increased progressively
(28% at 3 days, 59% at 7 days, and 90% at 14 days).
Immunohistochemistry revealed that the acidosis-induced increase in
NHE-3 abundance occurred in the apical membranes of the S1 and S2
segments of the proximal tubule and the thick ascending limb. NHE-3
mRNA abundance was not significantly increased in these animals,
while PEPCK and GAPDH mRNA abundances were significantly increased.
These studies demonstrate that the increase in Na/H antiporter
activity seen in metabolic acidosis, involves an increase in NHE-3
protein abundance which is distributed along the proximal tubule and
the thick ascending limb. In addition, these studies suggest that a
component of this adaptation is unrelated to changes in NHE-3 mRNA
abundance.
Received 9 February 1996; accepted in final form 11 July 1996.
APS Manuscript Number F44-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996