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.
Hussain
T
T
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, TX 77204-5515, USA.
Abdul-Wahab
R
R
Lokhandwala
M F
MF
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism*; D013268:Stimulation, Chemical
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase