Dopamine inhibits Na,H-exchanger via D-1-like receptor-mediated stimulation of protein kinase A in renal proximal tubules

Dopamine causes natriuresis and diuresis via activation of D-1-like recepto rs located in the renal proximal tubules. It is reported that this response to dopamine results from the inhibition of Na,H-exchanger and Na,K-ATPase. Earlier studies have suggested a role of protein kinase A (PKA) in the inh ibition of Na,H-exchanger, however, the effect of dopamine or the dopamine receptor subtype responsible for the stimulation of PKA has not been report ed. Present study was designed to examine the effect of dopamine and D-1-li ke receptor agonist, SKF 38393, on the stimulation of PKA activity in rat r enal proximal tubules. Dopamine and SKF 38393 (1 nM - 1 mu M) caused stimul ation of PKA activity, an effect which was antagonized by a D-1-like recept or antagonist, SCH 23390 (10 mu M) Stimulation of PKA activity was also see n with forskolin and di-butyryl cAMP. We also observed that dopamine and SK F 38393 inhibited Na,H-exchanger activity in the proximal tubules. This res ponse was blocked by SCH 23390 and Rp-cAMPS triethylamine, a selective inhi bitor of PKA. Similarly, forskolin and di-butyryl cAMP inhibited Na,H-excha nger activity. The data provide direct evidence showing that dopamine, thro ugh the activation of D-1-like receptors stimulates PKA activity which in t urn inhibits Na,H-exchanger in the proximal tubules.