Activation of D 3 Dopamine Receptor Decreases Angiotensin II Type 1 Receptor Expression in Rat Renal Proximal Tubule Cells

Abstract

The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D 3 dopamine receptor gene in mice produces renin-dependent hypertension. In rats, D 2 -like receptors reduce angiotensin II binding sites in renal proximal tubules (RPTs). Because the major D 2 -like receptor in RPTs is the D 3 receptor, we examined whether D 3 receptors regulate angiotensin II type 1 (AT 1 ) receptors in rat RPT cells. The effect of D 3 receptors on AT 1 receptors was studied in vitro and in vivo. The D 3 receptor agonist PD128907 decreased AT 1 receptor protein and mRNA in WKY RPT cells and increased it in SHR cells. PD128907 increased D 3 receptors in WKY cells but had no effect in SHR cells. D 3 /AT 1 receptors colocalized in RPT cells; D 3 receptor stimulation decreased the percent amount of D 3 receptors that coimmunoprecipitated with AT 1 receptors to a greater extent in WKY than in SHR cells. However, D 3 receptor stimulation did not change the percent amount of AT 1 receptors that coimmunoprecipitated with D 3 receptors in WKY cells and markedly decreased the coimmunoprecipitation in SHR cells. The D 3 receptor also regulated the AT 1 receptor in vivo because AT 1 receptor expression was increased in kidneys of D 3 receptor–null mice compared with wild type littermates. D 3 receptors may regulate AT 1 receptor function by direct interaction with and regulation of AT 1 receptor expression. One mechanism of hypertension may be related to increased renal expression of AT 1 receptors due decreased D 3 receptor regulation.