Receptor-mediated inhibition of renal Na+-K+-ATPase is associated with endocytosis of its α- and β-subunits

Alexander V. Chibalin, Adrian I. Katz, Per Olof Berggren, Alejandro M. Bertorello

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

The mechanisms involved in receptor-mediated inhibition of Na+ -K+ - ATPase remain poorly understood. In this study, we evaluate whether inhibition of proximal tubule Na+ -K+ -ATPase activity by dopamine is linked to its removal from the plasma membrane and internalization into defined intracellular compartments. Clathrin-coated vesicles were isolated by sucrose gradient centrifugation and negative lectin selection, and early and late endosomes were separated on a flotation gradient. Inhibition of Na+- K+-ATPase activity by dopamine, in contrast to its inhibition by ouabain, was accompanied by a sequential increase in the abundance of the α-subunit in clathrin-coated vesicles (1 min), early endosomes (2.5 min), and late endosomes (5 min), suggesting its stepwise translocation between these organelles. A similar pattern was found for the β-subunit. The increased incorporation of both subunits in all compartments was blocked by calphostin C. The results demonstrate that the dopamine-induced decrease in Na+- K+ATPase activity in proximal tubules is associated with internalization of its α- and β-subunits into early and late endosomes via a clathrin- dependent pathway and that this process is protein kinase C dependent. The presence of Na+-K+ATPase subunits in endosomes suggests that these compartments may constitute normal traffic reservoirs during pump degradation and/or synthesis.

Original languageEnglish (US)
Pages (from-to)C1458-C1465
JournalAmerican Journal of Physiology - Cell Physiology
Volume273
Issue number5 42-5
DOIs
StatePublished - 1997

Keywords

  • Actin-microtubule cytoskeleton
  • Clathrin vesicles
  • Dopamine
  • Endosomes
  • Protein kinase C
  • Proximal tubules

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

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