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Submitted on September 23, 2005
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. * To whom correspondence should be addressed. E-mail: cyzeng1{at}hotmail.com.
Abstract--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.
Revised on October 20, 2005
D3 Dopamine Receptor Directly Interacts With D1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells
Chunyu Zeng*;
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