Bromocriptine regulates angiotensin II response on sodium pump in proximal tubules

Dopamine and angiotensin II (Ang II) receptors have been reported to exhibit 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-mediated stimulation of Na,K-ATPase activity in the renal proximal tubules. Ang II (10(-13) to 10(-9) mol/L) stimulated Na,K-ATPase activity in the proximal tubules that was completely abolished when the tubules were pretreated with the D-2-like receptor agonist bromocriptine (1 mu moL/L) for 30 minutes. The effect of bromocriptine on Ang II, response was prevented by domperidone (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 Ang II (10 pmol/L) was also abolished in bromocriptine-pretreated tubules. Basal and forskolin-stimulated cAMP was not significantly different in bromocriptine-treated tubules compared with the control. [H-3]-Ang II binding sites (angiotensin type [AT(1)] receptors) were reduced by approximate to 65% in bromocriptine-treated proximal tubules, a result that was further substantiated by Western blot analysis revealing a 50% decrease in AT(1) receptors 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% decrease in G(i alpha 1) and G(i alpha 2) in the bromocriptine-treated proximal tubules. Bromocriptine (1 mu mol/L) alone stimulated Na,K-ATPase activity during the first 30 minutes of incubation, and thereafter the stimulation 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-ATPase 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.