Hyperphosphorylation of Na-pump contributes to defective renal dopamine response in old rats

Dopamine D-1-like receptor activation causes phosphorylation and inhibition of Na,K-ATPase (Na-pump) activity in the proximal tubules, which is associ ated with an increase in sodium excretion. It has been shown that dopamine and SKF 38393, a D-1-like receptor agonist, caused inhibition of Na,K-ATPas e activity in the proximal tubules of adult (6 mo) but not of old (24 mo) F ischer 344 rats. The present study demonstrated that SKF 38393 and PDBu, a phorbol ester and protein kinase C (PKC) activator, increased phosphorylati on of the alpha (1)-subunit of Na,K-ATPase in adult but not in old rats. In adult rats, SKF 38393-mediated phosphorylation was antagonized by SCH 2339 0, a D-1-like receptor antagonist. Similarly, Na,K-ATPase activity was inhi bited by SKF 38393 and PDBu in adult but not in old rats. The basal activit y of Na,K-ATPase was decreased and the basal phosphorylation state of the e nzyme was increased in old compared with adult rats. Basal activity of PKC was higher in old compared with adult rats, and SKF 38393 and PDBu stimulat ed PKC activity in adult but not in old rats. The conclusion is that the fa ilure of D-1-like receptor agonist and phorbol ester to stimulate PKC and i nhibit Na,K-ATPase activity in old rats is due, at least in part, to the hi gher basal PKC activity and Na,K-ATPase phosphorylation in old compared wit h adult rats.