Salt Loading Induces Redistribution of the Plasmalemmal Na/K-ATPase in Proximal Tubule CellsPharmaceutical Science and Research
AbstractBackground: We have reported that digitalis-like substances (cardiotonic steroids), including marinobufagenin (MBG), induce endocytosis of the plasmalemmal Na/K-ATPase in LLCPK1 cells. The current report addresses the potential relevance of plasmalemmal Na/K-ATPase redistribution to in vivo salt handling. Methods: Male Sprague-Dawley rats were given 1 week of a high salt (4.0% NaCl) or normal salt (0.4% NaCl) diet. Urinary sodium excretion, as well as MBG excretion, was monitored, and proximal tubules were isolated using a Percoll gradient method. Tubular 86Rb uptake, Na/K-ATPase enzymatic activity, and Na/K-ATPase a1 subunit density were determined. Results: The high salt diet increased urinary sodium (17.8 ± 1.8 vs. 2.5 ± 0.3 mEq/day, P < 0.01) and MBG excretion (104 ± 12 vs. 26 ± 4 pmol/day), and decreased proximal tubular 86Rb uptake (0.44 ± 0.07 vs. 1.00 ± 0.10, P < 0.01) and Na/KATPase enzymatic activity (5.1 ± 1.1 vs. 9.9 ± 1.6 lmol/mg pr/hr, P < 0.01) relative to the normal diet. Proximal tubular Na/KATPase a1 protein density was decreased in the plasmalemma fraction but increased in both early and late endosomes following the high salt diet. In rats fed a high salt diet, anti-MBG antibody caused a 60% reduction in urinary sodium excretion, substantial increases in proximal tubule 86Rb uptake, and Na/KATPase enzymatic activity, as well as significant decreases in the early and late endosomal Na/K-ATPase a1 protein content. Conclusion: These data suggest that redistribution of the proximal tubule Na/K-ATPase in response to endogenous cardiotonic steroids plays an important role in renal adaptation to salt loading.
Citation InformationThe version of record is available from the publisher at http://www.nature.com/ki/journal/v67/n5/pdf/4495253a.pdf. Copyright © 2005 by the International Society of Nephrology. All rights reserved. doi:10.1111/j.1523-1755.2005.00285.x