Phosphorylated Mr 32,000 dopamine- and cAMP-regulated phosphoprotein inhibits Na+,K(+)-ATPase activity in renal tubule cells.
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.
Aperia
A
A
Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
Fryckstedt
J
J
Svensson
L
L
Hemmings
H C
HC
Nairn
A C
AC
Greengard
P
P
D000595:Amino Acid Sequence; D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D007679:Kidney Medulla / Q000201:enzymology*; D007684:Kidney Tubules / Q000201:enzymology*; D007700:Kinetics; D008138:Loop of Henle / Q000201:enzymology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010748:Phosphopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010750:Phosphoproteins / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010748:Phosphopeptides; D010750:Phosphoproteins; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine