title: Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells.
abstract: BACKGROUND
  We have reported that digitalis-like substances (cardiotonic steroids), including marinobufagenin (MBG), induce 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 alpha1 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 micromol/mg pr/hr, P < 0.01) relative to the normal diet. Proximal tubular Na/K-ATPase alpha1 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 (86)Rb uptake, and Na/K-ATPase enzymatic activity, as well as significant decreases in the early and late endosomal Na/K-ATPase alpha1 protein content.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Medical College of Ohio, Toledo, Ohio 43614-5089, USA.
authors.forename: Sankaridrug M
authors.initials: SM
authors.lastname: Periyasamy
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Feras
authors.initials: F
authors.lastname: Tanta
authors.forename: Besher
authors.initials: B
authors.lastname: Kabak
authors.forename: Brent
authors.initials: B
authors.lastname: Wakefield
authors.forename: Deepak
authors.initials: D
authors.lastname: Malhotra
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: Alaa
authors.initials: A
authors.lastname: Nadoor
authors.forename: Olga V
authors.initials: OV
authors.lastname: Fedorova
authors.forename: William
authors.initials: W
authors.lastname: Gunning
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
authors.forename: Alexei Y
authors.initials: AY
authors.lastname: Bagrov
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002018:Bufanolides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000652:urine; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009318:Natriuresis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D000906:Antibodies; D002018:Bufanolides; D012982:Sodium, Dietary; C093896:marinobufagenin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase