Bromocriptine stimulates Na+,K+-ATPase in renal proximal tubules via the cAMP pathway

The present study was undertaken to examine the effect of dopamine D-2 receptor activation on Na+,K+-ATPase activity in rat renal proximal tubule suspension. Bromocriptine, a dopamine D-2 receptor agonist, produced a concentration (10(-9)-10(-5) M) dependent stimulation of Na+,K+-ATPase activity which was antagonized by pretreating the tubules with domperidone (1 mu M), a dopamine D-2 receptor antagonist. Forskolin (1 mu M), a direct activator of adenylyl cyclase, inhibited Na+,K+-ATPase activity and reversed the stimulation of Na+,K+-ATPase activity induced by bromocriptine. Pertussis toxin (200 ng/ml) treatment also abolished the bromocriptine-induced stimulation of Na+,K+-ATPase activity. Bromocriptine attenuated forskolin-stimulated cAMP accumulation which was blocked by pertussis toxin treatment of the tubules. The data suggest that dopamine D-2 receptor activation by bromocriptine leads to stimulation of Na+,K+-ATPase activity which may be mediated through a pertussis-sensitive G protein and inhibition of adenylyl cyclase in rat renal proximal tubules. (C) 1997 Elsevier Science B.V.