Gα 12 - and Gα 13 -Protein Subunit Linkage of D 5 Dopamine Receptors in the Nephron

Publisher Website
Google Scholar
Abstract
The roles of the G-protein α-subunits, G s , G i , and G q/11 , in the signal transduction of the D 1 -like dopamine receptors, D 1 and D 5 , have been deciphered. Gα 12 and Gα 13 , members of the 4th family of G protein subunits, are not linked with D 1 receptors, and their linkage to D 5 receptors is not known. Therefore, we studied the expression of Gα 12 and Gα 13 and interaction with D 5 dopamine receptors in the kidney from normotensive Wistar-Kyoto (WKY) rats and D 5 receptor-transfected HEK293 cells. Gα 12 and Gα 13 were found in the proximal tubule, distal convoluted tubule, and artery and vein in the WKY rat kidney. Whereas Gα 12 was expressed in the ascending limb of Henle, Gα 13 was expressed in the collecting duct and juxtaglomerular cells. In renal proximal tubules, Gα 12 and Gα 13 , as with D 5 receptors, were expressed in brush border membranes. Laser confocal microscopy revealed the colocalization of D 5 receptors with Gα 12 and Gα 13 in rat renal brush border membranes, immortalized rat renal proximal tubule cells, and D 5 receptor-transfected HEK293 cells. In these cells, a D 1 -like agonist, fenoldopam, increased the association of Gα 12 and Gα 13 with D 5 receptors, results that were corroborated by immunoprecipitation experiments. We conclude that although both D 1 and D 5 receptors are linked to Gαs, they are differentially linked to Gα 12 and Gα 13 . The consequences of the differential G-protein subunit linkage on D 1 - and D 5 -mediated sodium transport remains to be determined.