Hormonal-dependent recruitment of Na+,K+-ATPase to the plasmalemma is mediated by PKC beta and modulated by [Na+]i

Br J Pharmacol. 2002 Dec;137(8):1380-6. doi: 10.1038/sj.bjp.0704962.


1. The present study demonstrates that stimulation of hormonal receptors of proximal tubule cells with the serotonin-agonist 8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) induces an augmentation of Na(+),K(+)-ATPase activity that results from the recruitment of enzyme molecules to the plasmalemma. 2. Cells expressing the rodent wild-type Na(+),K(+)-ATPase alpha-subunit had the same basal Na(+),K(+)-ATPase activity as cells expressing the alpha-subunit S11A or S18A mutants, but stimulation of Na(+),K(+)-ATPase activity was completely abolished in either mutant. 3. 8-OH-DPAT treatment of OK cells led to PKC(beta)-dependent phosphorylation of the alpha-subunit Ser-11 and Ser-18 residues, and determination of enzyme activity with the S11A and S18A mutants indicated that both residues are essential for the agonist-dependent stimulation of Na(+),K(+)-ATPase activity. 4. When cells were treated with both dopamine and 8-OH-DPAT, an activation of Na(+),K(+)-ATPase was observed at basal intracellular sodium concentration (approximately 9 mM), and this activation was gradually reduced and became a significant inhibition as the concentration of intracellular sodium gradually increased from 9 to 19 mM. Thus, besides the antagonistic effects of dopamine and 8-OH-DPAT, intracellular sodium modulates whether an activation or an inhibition of Na(+),K(+)-ATPase is produced.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / enzymology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Intracellular Fluid / enzymology
  • Intracellular Fluid / metabolism*
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / enzymology
  • Opossums
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Receptors, Cell Surface / metabolism*
  • Receptors, Serotonin / metabolism
  • Sodium / metabolism
  • Sodium / physiology*
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Enzyme Inhibitors
  • Receptors, Cell Surface
  • Receptors, Serotonin
  • Sodium
  • Protein Kinase C
  • Protein Kinase C beta
  • Sodium-Potassium-Exchanging ATPase