Sheikh-Hamad D, Wang Y P, Jo O D, Yanagawa N
Division of Nephrology, Sepulveda Department of Veterans Affairs Medical Center 91343.
Am J Physiol. 1993 Apr;264(4 Pt 2):F737-43. doi: 10.1152/ajprenal.1993.264.4.F737.
In the present study, we examined the effects of dopamine and angiotensin II (ANG II) in renal brush-border membrane (BBM). With isolated BBM vesicles, dopamine (> 10(-4) M) directly inhibited BBM 22Na+ uptake and activated phospholipase C (PLC). These effects were mimicked by DA1 agonist but not DA2 agonist and were prevented by DA1 antagonist but not DA2 antagonist, indicating the involvement of DA1 receptors. In contrast to dopamine, ANG II directly stimulated BBM 22Na+ uptake and activated BBM phospholipase A2 (PLA2). Neither dopamine nor ANG II altered BBM adenosine 3',5'-cyclic monophosphate content. In the presence of dopamine, ANG II failed to stimulate BBM Na+ uptake and PLA2. However, both DA1 and DA2 agonists similarly abrogated the actions of ANG II, and both DA1 and DA2 antagonists were required to restore ANG II actions in the presence of dopamine, indicating the involvement of both DA1 and DA2 receptors in the antagonistic effect of dopamine. Dopamine, as well as DA1 or DA2 agonists, also lowered 125I-ANG II BBM binding. In summary, these results show that, in renal BBM, dopamine impedes ANG II receptor binding and antagonizes the stimulatory effects of ANG II on Na+ uptake and PLA2. This occurred through both DA1 and DA2 receptors and independent of DA1 effects on BBM Na+ uptake or PLC.
在本研究中，我们检测了多巴胺和血管紧张素II（ANG II）对肾刷状缘膜（BBM）的影响。对于分离出的BBM囊泡，多巴胺（>10⁻⁴ M）直接抑制BBM对²²Na⁺的摄取并激活磷脂酶C（PLC）。DA1激动剂可模拟这些作用，而DA2激动剂则不能，且DA1拮抗剂可阻止这些作用，而DA2拮抗剂则不能，这表明DA1受体参与其中。与多巴胺相反，ANG II直接刺激BBM对²²Na⁺的摄取并激活BBM磷脂酶A2（PLA2）。多巴胺和ANG II均未改变BBM中3',5'-环磷酸腺苷的含量。在存在多巴胺的情况下，ANG II未能刺激BBM对Na⁺的摄取和PLA2。然而，DA1和DA2激动剂均同样消除了ANG II的作用，并且在存在多巴胺的情况下，需要DA1和DA2拮抗剂才能恢复ANG II的作用，这表明DA1和DA2受体均参与了多巴胺的拮抗作用。多巴胺以及DA1或DA2激动剂也降低了¹²⁵I-ANG II与BBM的结合。总之，这些结果表明，在肾BBM中，多巴胺阻碍ANG II受体结合，并拮抗ANG II对Na⁺摄取和PLA2的刺激作用。这是通过DA1和DA2受体发生的，且独立于DA1对BBM Na⁺摄取或PLC的作用。
