D 3 Dopamine Receptor Directly Interacts With D 1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells

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Abstract
D 3 receptors act synergistically with D 1 receptors to inhibit sodium transport in renal proximal tubules; however, the mechanism by which this occurs is not known. Because dopamine receptor subtypes can regulate and interact with each other, we studied the interaction of D 3 and D 1 receptors in rat renal proximal tubule (RPT) cells. The D 3 agonist PD128907 increased the immunoreactive expression of D 1 receptors in a concentration- and time-dependent manner; these effects were blocked by the D 3 antagonist U99194A. PD128907 also transiently (15 minutes) increased the amount of cell surface membrane D 1 receptors. Laser confocal immunofluorescence microscopy showed that D 3 receptor and D 1 receptor colocalized in RPT cells more distinctly in Wistar-Kyoto rats than in spontaneously hypertensive rats (SHRs). In addition, D 3 and D 1 receptors could be coimmunoprecipitated, and this interaction was increased after D 3 receptor agonist stimulation for 24 hours in Wistar-Kyoto rats but not in SHRs. We propose that the synergistic effects of D 3 and D 1 receptors may be caused by a D 3 receptor–mediated increase in total, as well as cell surface membrane D 1 receptor expression, and direct D 3 and D 1 receptor interaction, both of which are impaired in SHRs.