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 M(r) 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 phosphorylated DARPP-32 is a component of the mechanism by which dopamine regulates urinary Na+ excretion.