Bromocriptine regulates angiotensin II response on sodium pump in proximaltubules

Dopamine and angiotensin II (Ang II) receptors have been reported to exhibi t an interaction in renal proximal tubules, The present study was designed to investigate the regulation by a D-2-like dopamine receptor of Ang II-med iated stimulation of Na,K-ATPase activity in the renal proximal tubules. An g II (10(-13) to 10(-9) mol/L) stimulated Na,K-ATPase activity in the proxi mal tubules that was completely abolished when the tubules were pretreated with the D-2-like receptor agonist bromocriptine (1 mu moL/L) for 30 minute s. The effect of bromocriptine on Ang II, response was prevented by domperi done (1 mu mol/L), a D-2-like dopamine receptor antagonist. Similarly, the inhibition of forskolin (1 mu mol/L)-induced cAMP accumulation caused by An g II (10 pmol/L) was also abolished in bromocriptine-pretreated tubules. Ba sal and forskolin-stimulated cAMP was not significantly different in bromoc riptine-treated tubules compared with the control. [H-3]-Ang II binding sit es (angiotensin type [AT(1)] receptors) were reduced by approximate to 65% in bromocriptine-treated proximal tubules, a result that was further substa ntiated by Western blot analysis revealing a 50% decrease in AT(1) receptor s in bromocriptine-treated tubules compared with the control. Western blot analysis of G proteins revealed a 2-fold increase in G(s alpha) and a 20% d ecrease in G(i alpha 1) and G(i alpha 2) in the bromocriptine-treated proxi mal tubules. Bromocriptine (1 mu mol/L) alone stimulated Na,K-ATPase activi ty during the first 30 minutes of incubation, and thereafter the stimulatio n fell to the basal level. Similarly, bromocriptine-mediated inhibition of cAMP lasted only up to 20 minutes. The data suggest that preactivation of D -2-like dopamine receptors abolishes Ang II-mediated stimulation of Na,K-AT Pase activity and inhibition of cAMP accumulation. This phenomenon may be a consequence of a decrease in AT(1) receptors and alterations in G protein levels in the proximal tubules, We propose that such a regulation of Ang II response by bromocriptine is the result of heterologous desensitization of the D-2-like receptor system.