INHIBITION OF NA+,K+-ATPASE IN RAT RENAL PROXIMAL TUBULES BY DOPAMINE INVOLVED DA-1 RECEPTOR ACTIVATION

Endogenous kidney dopamine (DA) causes natriuresis and diuresis, at least partly, via inhibition of proximal tubular Na+,K+-ATPase. The present study was done to identify the dopamine receptor subtype(s) involved in dopamine-induced inhibition of Na+,K+-ATPase activity. Suspensions of renal proximal tubules from Sprague-Dawley rats were incubated with dopamine, the DA-1 receptor agonist fenoldopam or the DA-2 receptor agonist SK&F 89124 in the presence or absence of either the DA-1 receptor antagonist SCH 23390 or the DA-2 receptor antagonist domperidone. Dopamine and fenoldopam (10(-5) to 10(-8) mol/l) produced a concentration-dependent inhibition of Na+,K+-ATPase activity. However, SK&F 89124 failed to produce any significant effect over the same concentration range. Incubation with fenoldopam (10(-5) to 10(-8) mol/l) in the presence of SK&F 89124 (10(-6) mol/l) inhibited Na+,K+-ATPase activity to a degree similar to that with fenoldopam alone. Furthermore, DA-induced inhibition of Na+,K+-ATPase activity was attenuated by SCH 23390, but not by domperidone. Since alpha-adrenoceptor activation is reported to stimulate Na+,K+-ATPase activity and, at higher concentrations, dopamine also acts as an alpha-adrenoceptor agonist, the potential opposing effect from alpha-adrenoceptor activation on DA-induced inhibition of Na+,K+-ATPase activity was investigated by using the alpha-adrenoceptor blocker phentolamine. We found that, in the lower concentration range (10(-5) to 10(-7) mol/l), dopamine-induced inhibition of Na+,K+-ATPase activity in the presence of phentolamine was similar in magnitude to that observed with dopamine alone. However, at the highest concentration used (10(-4) mol/l), dopamine produced a significantly larger degree of inhibition of Na+,K+-ATPase activity in the presence of phentolamine. These results indicate that the DA-1 dopamine receptor subtype, but not the DA-2 receptor subtype, is involved in dopamine-mediated inhibition of Na+,K+-ATPase. At higher concentrations of dopamine, the DA-1 receptor-mediated inhibitory effect on Na+,K+-ATPase activity may be partly opposed by a simultaneous alpha-adrenoceptor-mediated stimulation of the activity of this enzyme.