Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells

Autor: Deepak Malhotra, Olga V. Fedorova, Alaa Nadoor, David J. Kennedy, Jiang Liu, Feras Tanta, Zijian Xie, Sankaridrug M. Periyasamy, Besher Kabak, Alexei Y. Bagrov, Brent Wakefield, Joseph I. Shapiro, William T. Gunning
Rok vydání: 2005
Předmět:
Zdroj: Kidney international. 67(5)
ISSN: 0085-2538
Popis: Salt loading induces redistribution of the plasmalemmal Na/K- ATPase in proximal tubule cells. Background. We have reported that digitalis-like substances (cardiotonic steroids), including marinobufagenin (MBG), in- duce endocytosis of the plasmalemmal Na/K-ATPase in LLC- PK1 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 86 Rb 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 86 Rb uptake (0.44 ± 0.07 vs. 1.00 ± 0.10, P < 0.01) and Na/K- ATPase 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/K- ATPase a1 protein density was decreased in the plasmalemma fraction but increased in both early and late endosomes fol- lowing 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 86 Rb uptake, and Na/K- ATPase 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 car- diotonic steroids plays an important role in renal adaptation to salt loading.
Databáze: OpenAIRE