D 3 dopamine receptor regulation of D 5 receptor expression and function in renal proximal tubule cells

Document Type

Journal Article

Publication Date

6-1-2012

Journal

Hypertension Research

Volume

35

Issue

6

DOI

10.1038/hr.2012.11

Keywords

kidney; rats, normotensive; rats, spontaneously hypertensive; receptor, dopamine

Abstract

Dopamine receptor, via D 1-like and D 2-like receptors, increases sodium excretion in kidney. We have reported positive interactions between D 3 and D 1 receptors in renal proximal tubule (RPT) cells. These reports, however do not preclude that there may be also interaction between D 3 and D 5 receptors, because of the lack of selective D 1 and D 5 receptor agonists or antagonists. We hypothesize that D 3 receptors can regulate D 5 receptors, and that D 3 receptor regulation of D 5 receptors in RPTs is impaired in spontaneously hypertensive rats (SHRs). It showed that a D 3 receptor agonist, PD128907, by the activation of protein kinase C activity, increased the expression of D 5 receptors in a concentration- and time-dependent manner in RPT cells from Wistar-Kyoto (WKY) rats. The stimulatory effect of the D 3 receptor on D 5 receptor expression was impaired in RPT cells from SHRs. The effect of D 3 receptor on D 5 receptor is functionally relevant; stimulation of D 5 receptor decreases Na +-K + adenosine triphosphatase (ATPase) activity in WKY cells. Pretreatment with D 3 receptor agonist for 24 h enhances the D 5 receptor expression and D 5 receptor-mediated inhibitory effect on Na +-K + ATPase activity in WKY cells, but decreases them in SHR cells. The effect of D 3 receptor on D 5 receptor expression and function was also confirmed in the D 5 receptor-transfected HEK293 cells. It indicates that activation of D 3 receptor increases D 5 receptor expression and function. Altered regulation of D 3 receptor on D 5 receptors may have a role in the pathogenesis of hypertension. © 2012 The Japanese Society of Hypertension All rights reserved.

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