Role of Gα 12-and Gα 13-protein subunit linkage of D 3 dopamine receptors in the natriuretic effect of D 3 dopamine receptor in kidney

Document Type

Journal Article

Publication Date

9-1-2011

Journal

Hypertension Research

Volume

34

Issue

9

DOI

10.1038/hr.2011.70

Keywords

Dopamine; G proteins; kidney; natriuresis; receptors

Abstract

The D 3 dopamine receptor is the major D 2-like receptor that regulates sodium transport in the renal proximal tubule (RPT) and helps maintain blood pressure in the normal range. In Wistar-Kyoto (WKY) rats chronically fed high-salt diet, the intrarenal arterial infusion of a D 3 receptor agonist, PD128907, increased absolute and fractional sodium excretion. We have reported that Gα 12 and Gα 13, which participate in the signal transduction of the D 5 receptor, are expressed in RPTs. As the D 3 receptor is also expressed in RPTs, we hypothesized that it may also interact with Gα 12/Gα 13 in RPTs from WKY rats. There were co-localization and co-immunoprecipitation of D 3 receptor and Gα 12/Gα 13 in renal brush border membranes (BBMs) and RPT cells. The intrarenal infusion of PD128907 (1 μg kg -1 min -1) that increased sodium excretion also increased the co-immunoprecipitations of D 3/Gα 12 and D 3/Gα 13 in renal BBMs; their co-immunoprecipitation was confirmed in RPT cells. As Gα 12 and Gα 13 increase sodium pump and transporter activity (for example, Na +-K +-ATPase, NHE3), an increased association of D 3 receptors with Gα 12/Gα 13 receptors after D 3 receptor activation may be a mechanism to prevent Gα 12/Gα 13-mediated stimulation of sodium transport (and thus enhance natriuresis). We conclude that a D 3 receptor interaction with Gα 12/Gα 13 that increases sodium excretion may have a role in the regulation of blood pressure. © 2011 The Japanese Society of Hypertension All rights reserved.

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