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

The present study was undertaken to examine the effect of dopamine D2 receptor activation on Na+,K(+)-ATPase activity in rat renal proximal tubule suspension. Bromocriptine, a dopamine D2 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 microM), a dopamine D2 receptor antagonist. Forskolin (1 microM), 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 D2 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.