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(Hypertension. 2003;41:604.)
© 2003 American Heart Association, Inc.

Scientific Contributions

G₁₂- and G₁₃-Protein Subunit Linkage of D₅ Dopamine Receptors in the Nephron

Shaopeng Zheng; Peiying Yu; Chunyu Zeng; Zheng Wang; Zhiwei Yang; Peter M. Andrews; Robin A. Felder; Pedro A. Jose

From the Departments of Pediatrics (S.Z., P.Y., C.Z., Z.W., Z.Y., P.A.J.), Physiology and Biophysics (Z.Y., P.A.J.), and Cell Biology (P.M.A.), Georgetown University Medical Center, Washington, DC, and the Department of Pathology, The University of Virginia Health Sciences Center (R.A.F.), Charlottesville, Va.

Correspondence to Dr Pedro A. Jose, Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007. E-mail pjose01{at}georgetown.edu

The roles of the G-protein -subunits, G_s, G_i, and G_q/11, in the signal transduction of the D₁-like dopamine receptors, D₁ and D₅, have been deciphered. G₁₂ and G₁₃, members of the 4th family of G protein subunits, are not linked with D₁ receptors, and their linkage to D₅ receptors is not known. Therefore, we studied the expression of G₁₂ and G₁₃ and interaction with D₅ dopamine receptors in the kidney from normotensive Wistar-Kyoto (WKY) rats and D₅ receptor-transfected HEK293 cells. G₁₂ and G₁₃ were found in the proximal tubule, distal convoluted tubule, and artery and vein in the WKY rat kidney. Whereas G₁₂ was expressed in the ascending limb of Henle, G₁₃ was expressed in the collecting duct and juxtaglomerular cells. In renal proximal tubules, G₁₂ and G₁₃, as with D₅ receptors, were expressed in brush border membranes. Laser confocal microscopy revealed the colocalization of D₅ receptors with G₁₂ and G₁₃ in rat renal brush border membranes, immortalized rat renal proximal tubule cells, and D₅ receptor-transfected HEK293 cells. In these cells, a D₁-like agonist, fenoldopam, increased the association of G₁₂ and G₁₃ with D₅ receptors, results that were corroborated by immunoprecipitation experiments. We conclude that although both D₁ and D₅ receptors are linked to Gs, they are differentially linked to G₁₂ and G₁₃. The consequences of the differential G-protein subunit linkage on D₁- and D₅-mediated sodium transport remains to be determined.

Key Words: receptors, dopamine • G proteins • juxtaglomerular apparatus • immunohistochemistry

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