Dopamine Downregulation of Proximal Tubule AT

Systemic and/or locally produced angiotensin II stimulates salt and water reabsorption in the renal proximal tubule. In vivo, dopamine (DA) may serve as a counterregulatory hormone to angiotensin II’s acute actions on the proximal tubule. We examined whether dopamine modulates AT 1 receptor expression in cultured proximal tubule cells (RPTC) expressing DA 1 receptors. Dopamine decreased basal RPTC AT 1 receptor mRNA levels by 67 6 7% ( n 5 10; P , 0.005) and decreased 125 I-angiotensin II binding by 41 6 7% ( n 5 4; P , 0.05). The DA 1 -specific agonist, SKF38393 decreased basal AT 1 receptor mRNA levels (65 6 5% inhibition; n 5 5; P , 0.025), and the DA 1 -specific antagonist, SCH23390 reversed dopamine’s inhibition of AT 1 receptor mRNA expression (24 6 10% inhibition; n 5 8; NS) and angiotensin II binding (5 6 15%; n 5 4; NS). DA 2 -specific antagonists were ineffective. In rats given L-DOPA in the drinking water for 5 d, there were decreases in both proximal tubule AT 1 receptor mRNA expression (80 6 5%; n 5 6; P , 0.005) and specific [ 125 I] Ang II binding (control: 0.74 6 0.13 fmol/mg pro vs. 0.40 6 0.63 fmol/mg pro; n 5 5; P , 0.05). In summary, dopamine, acting through DA 1 receptors, decreased AT 1 receptor expression in proximal tubule, an effect likely mediated by increased intracellular cAMP levels. Local dopamine production also led to decreased AT 1 receptor expression, suggesting dopamine may reset sensitivity of the proximal tubule to angiotensin II. ( J . Clin . Invest . 1996. 97:2745–2752.)