Renal na/h exchanger isoforms and their regulation by thyroid hormone. Azuma, Kay K., Daniel F. Balkovetz, Clara E. Magyar, Leslie Lescale -Matys, Yibin Zhang, Regine Chambrey, David G. Warnock, and Alicia A. McDonough. Department of Physiology and Biophysics, University of Southern California School of Medicine, and Departments of Medicine and Physiology and Biophysics, Nephrology Research and Training Center, Vascular Biology and Hypertension Program, University of Alabama at Birmingham and Department of Veterans Affairs
APStracts 2:0306C, 1995.
Sodium crosses the luminal membrane of the proximal tubule primarily via Na+- H+ exchange (NHE), and NHE activity is influenced by thyroid status. Pharmacological, immunological, and kinetic studies indicate multiple isoforms of NHE, and four full length cDNAs have been cloned to date. The aims of this study were to determine which NHE mRNAs (NHE-1, -2, -3 and -4) were expressed in the rat proximal tubule, the relative abundance of each in the renal cortex, and the effect of thyroid status on their expression. By blot hybridization of poly A+ RNA all NHE isoform mRNAs were detected in the rat renal cortex, NHE -1, -2, and -3 in proximal tubule, and NHE-1 and -3 in LLC-PK1 cells. NHE-3 mRNA abundance was four-fold higher than the other three isoforms in renal cortex. The effect of thyroid status was assessed in renal cortex from euthyroid, hypothyroid and hyperthyroid rats. While none of the NHE mRNA levels were altered in the transition from euthyroid to hypothyroid, both NHE-2 and NHE-3 mRNA levels increased 1.5 fold in the transition from hypo- to hyperthyroid. NHE-3 protein, measured by immunoblot using an NHE-3 specific antibody, was detected at 83-85 kDa in renal cortex, and co-distributed on sorbitol gradients with the brush border marker alkaline phosphatase. No significant difference in NHE-3 protein abundance was detected between hypothyroid and hyperthyroid rats. In conclusion, in the renal cortex the NHE-3 isoform predominates at the mRNA level, is expressed in apical membranes, and increases at the mRNA but not the protein levels in response to thyroid hormone treatment suggesting parallel changes in synthesis and turnover of NHE-3 by thyroid hormone. 

Received 12 May 1994; accepted in final form 10 August 1995.
APS Manuscript Number C289-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.