Phosphorylated Mr 32,000 dopamine- and cAMP-regulated phosphoprotein inhibits Na+,K(+)-ATPase activity in renal tubule cells

Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2798-801. doi: 10.1073/pnas.88.7.2798.


Dopamine inhibits Na+,K(+)-ATPase activity in several renal tubule segments and thereby regulates urinary Na+ excretion. We now show that a phosphopeptide of 31 amino acids, corresponding to residues 8-38 of the protein phosphatase inhibitor DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), mimics the inhibitory action of dopamine on Na+,K(+)-ATPase activity in renal tubule cells from the ascending limb of the loop of Henle. The dephosphorylated form of the peptide is ineffective. The results indicate that dopamine acts through a protein phosphorylation pathway to regulate the activity of an ion pump. In addition, the data suggest that inhibition of protein phosphatase 1 by phophorylated DARPP-32 is a component of the mechanism by which dopamine regulates urinary Na+ excretion.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dopamine / pharmacology
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Kidney Medulla / enzymology*
  • Kidney Tubules / enzymology*
  • Kinetics
  • Loop of Henle / enzymology*
  • Models, Biological
  • Molecular Sequence Data
  • Molecular Weight
  • Nerve Tissue Proteins / pharmacology*
  • Phosphopeptides / chemical synthesis*
  • Phosphopeptides / pharmacology
  • Phosphoproteins / pharmacology*
  • Phosphorylation
  • Rats
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*


  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Nerve Tissue Proteins
  • Phosphopeptides
  • Phosphoproteins
  • Sodium-Potassium-Exchanging ATPase
  • Dopamine