DOPAMINE ANTAGONIZES THE ACTIONS OF ANGIOTENSIN-II IN RENAL BRUSH-BORDER MEMBRANE

In the present study, we examined the effects of dopamine and angioten sin II (ANG II) in renal brush-border membrane (BBM). With isolated BB M vesicles, dopamine (>10(-4) M) directly inhibited BBM Na-22+ uptake and activated phospholipase C (PLC). These effects were mimicked by DA 1 agonist but not DA2 agonist and were prevented by DA1 antagonist but not DA2 antagonist, indicating the involvement of DA1 receptors. In c ontrast to dopamine, ANG II directly stimulated BBM Na-22+ uptake and activated BBM phospholipase A2 (PLA2). Neither dopamine nor ANG II alt ered BBM adenosine 3',5'-cyclic monophosphate content. In the presence of dopamine, ANG II failed to stimulate BBM Na+ uptake and PLA2. Howe ver, both DA1 and DA2 agonists similarly abrogated the actions of ANG II, and both DA1 and DA2 antagonists were required to restore ANG II a ctions in the presence of dopamine, indicating the involvement of both DA1 and DA2 receptors in the antagonistic effect of dopamine. Dopamin e, as well as DA1 or DA2 agonists, also lowered I-125-ANG II BBM bindi ng. In summary, these results show that, in renal BBM, dopamine impede s ANG II receptor binding and antagonizes the stimulatory effects of A NG II on Na+ uptake and PLA2. This occurred through both DA1 and DA2 r eceptors and independent of DA1 effects on BBM Na+ uptake or PLC.