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Little is known regarding how the kidney shifts from a sodium and water reclaiming state (antinatriuresis) to a state where sodium and water are eliminated (natriuresis). In human renal proximal tubule cells, sodium reabsorption is decreased by the dopamine D1-like receptors (D1R/D5R) and the angiotensin type 2 receptor (AT2R), whereas the angiotensin type 1 receptor increases sodium reabsorption. Aberrant control of these opposing systems is thought to lead to sodium retention and, subsequently, hypertension. We show that D1R/D5R stimulation increased plasma membrane AT2R 4-fold via a D1R-mediated, cAMP-coupled, and protein phosphatase 2A–dependent specific signaling pathway. D1R/D5R stimulation also reduced the ability of angiotensin II to stimulate phospho-extracellular signal–regulated kinase, an effect that was partially reversed by an AT2R antagonist. Fenoldopam did not increase AT2R recruitment in renal proximal tubule cells with D1Rs uncoupled from adenylyl cyclase, suggesting a role of cAMP in mediating these events. D1Rs and AT2Rs heterodimerized and cooperatively increased cAMP and cGMP production, protein phosphatase 2A activation, sodium-potassium-ATPase internalization, and sodium transport inhibition. These studies shed new light on the regulation of renal sodium transport by the dopaminergic and angiotensin systems and potential new therapeutic targets for selectively treating hypertension.