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(Hypertension. 2006;47:573.)
© 2006 American Heart Association, Inc.

Part 2 Original Articles

D₃ Dopamine Receptor Directly Interacts With D₁ Dopamine Receptor in Immortalized Renal Proximal Tubule Cells

Chunyu Zeng; Zheng Wang; Hewang Li; Peiying Yu; Shaopeng Zheng; Lijuan Wu; Laureano D. Asico; Ulrich Hopfer; Gilbert M. Eisner; Robin A. Felder; Pedro A. Jose

From the Department of Cardiology (C.Z., L.W.), Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China; Departments of Pediatrics (C.Z., Z.W., H.L., P.Y., S.Z., L.D.Z., P.A.J.), Physiology and Biophysics (P.A.J.), and Internal Medicine (G.M.E.), Georgetown University Medical Center, Washington, DC; Department of Physiology and Biophysics (U.H.), Case Western Reserve School of Medicine, Cleveland, Ohio; and Department of Pathology (R.A.F.), Virginia University for the Health Sciences, Charlottesville, Va.

Correspondence to Chunyu Zeng, Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China. E-mail cyzeng1{at}hotmail.com

D₃ receptors act synergistically with D₁ 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 D₃ and D₁ receptors in rat renal proximal tubule (RPT) cells. The D₃ agonist PD128907 increased the immunoreactive expression of D₁ receptors in a concentration- and time-dependent manner; these effects were blocked by the D₃ antagonist U99194A. PD128907 also transiently (15 minutes) increased the amount of cell surface membrane D₁ receptors. Laser confocal immunofluorescence microscopy showed that D₃ receptor and D₁ receptor colocalized in RPT cells more distinctly in Wistar-Kyoto rats than in spontaneously hypertensive rats (SHRs). In addition, D₃ and D₁ receptors could be coimmunoprecipitated, and this interaction was increased after D₃ receptor agonist stimulation for 24 hours in Wistar-Kyoto rats but not in SHRs. We propose that the synergistic effects of D₃ and D₁ receptors may be caused by a D₃ receptor–mediated increase in total, as well as cell surface membrane D₁ receptor expression, and direct D₃ and D₁ receptor interaction, both of which are impaired in SHRs.

Key Words: receptors, dopamine • hypertension, essential • kidney • microscopy, confocal

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