D3 dopamine receptor regulation of D5 receptor expression and function in renal proximal tubule cells

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 D3 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. Hypertension Research (2012) 35, 639-647; doi:10.1038/hr.2012.11; published online 2 February 2012