Published Online
on February 7, 2005

A more recent version of this article appeared on April 1, 2005

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Submitted on October 10, 2004
Revised on November 1, 2004

Interaction of Angiotensin II Type 1 and D₅ Dopamine Receptors in Renal Proximal Tubule Cells

Chunyu Zeng^*; Zhiwei Yang; Zheng Wang; John Jones; Xiaoyan Wang; Joanna Altea; Amy J. Mangrum; Ulrich Hopfer; David R. Sibley; Gilbert M. Eisner; Robin A. Felder; and Pedro A. Jose

From the Department of Cardiology (C.Z.), Daping Hospital, Third Military Medical University, Chongqing, P.R. China; Departments of Pediatrics (Z.Y., Z.W., J.J., X.W., J.A., P.A.J.), Physiology and Biophysics (Z.Y., P.A.J.), and Medicine (G.M.E.), Georgetown University Medical Center, Washington, DC; Departments of Medicine (A.J.M.) and Pathology (R.A.F.), University of Virginia Health Sciences Center, Charlottesville; Department of Physiology and Biophysics (U.H.), Case Western Reserve School of Medicine, Cleveland, Ohio; and Molecular Neuropharmacology Section (D.R.S.), National Institute of Neurological Disorders and Stroke/NIH, Bethesda, Md.

^* To whom correspondence should be addressed. E-mail: cyzeng1{at}hotmail.com.

Abstract--Angiotensin II type 1 (AT₁) receptor and D₁ and D₃ dopamine receptors directly interact in renal proximal tubule (RPT) cells from normotensive Wistar-Kyoto rats (WKY). There is indirect evidence for a D₅ and AT₁ receptor interaction in WKY and spontaneously hypertensive rats (SHR). Therefore, we sought direct evidence of an interaction between AT₁ and D₅ receptors in RPT cells. D₅ and AT₁ receptors colocalized in WKY cells. Angiotensin II decreased D₅ receptors in WKY cells in a time- and concentration-dependent manner (EC₅₀=2.7x10^-9 M; t_1/2=4.9 hours), effects that were blocked by an AT₁ receptor antagonist (losartan). In SHR, angiotensin II (10^-8 M/24 hours) also decreased D₅ receptors (0.96±0.08 versus 0.72±0.08; n=12) and to the same degree as in WKY cells (1.44±0.07 versus 0.92±0.08). However, basal D₅ receptors were decreased in SHR RPT cells (SHR 0.96±0.08; WKY 1.44±0.07; n=12 per strain; P<0.05) and renal brush border membranes of SHR compared with WKY (SHR 0.54±0.16 versus WKY 1.46±0.10; n=5 per strain; P<0.05). Angiotensin II decreased AT₁ receptor expression in WKY (1.00±0.04 versus 0.72±0.08; n=8; P<0.05) but increased it in SHR (0.96±0.04 versus 1.32±0.08; n=8; P<0.05). AT₁ and D₅ receptors also interacted in vivo; renal D₅ receptor protein was higher in mice lacking the AT_1A receptor (AT_1A-/-; 1.61±0.31; n=6) than in wild-type littermates used as controls (AT_1A+/+; 0.81±0.08; n=6; P<0.05), and renal cortical AT₁ receptor protein was higher in D₅ receptor null mice than in wild-type littermates (1.18±0.08 versus 0.84±0.07; n=4; P<0.05). We conclude that D₅ and AT₁ receptors interact with each other. Altered interactions between AT₁ and dopamine receptors may play a role in the pathogenesis of hypertension.

Key words: receptors, dopamine • receptors, angiotensin II • rats, spontaneously hypertensive • normotension • kidney

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