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

Dopamine receptor, via D1-like and D2-like receptors, increases sodium excretion in kidney. We have reported positive interactions between D3 and D1 receptors in renal proximal tubule (RPT) cells. These reports, however do not preclude that there may be also interaction between D3 and D5 receptors, because of the lack of selective D1 and D5 receptor agonists or antagonists. We hypothesize that D3 receptors can regulate D5 receptors, and that D3 receptor regulation of D5 receptors in RPTs is impaired in spontaneously hypertensive rats (SHRs). It showed that a D3 receptor agonist, PD128907, by the activation of protein kinase C activity, increased the expression of D5 receptors in a concentration- and time-dependent manner in RPT cells from Wistar-Kyoto (WKY) rats. The stimulatory effect of the D3 receptor on D5 receptor expression was impaired in RPT cells from SHRs. The effect of D3 receptor on D5 receptor is functionally relevant; stimulation of D5 receptor decreases Na+–K+ adenosine triphosphatase (ATPase) activity in WKY cells. Pretreatment with D3 receptor agonist for 24 h enhances the D5 receptor expression and D5 receptor-mediated inhibitory effect on Na+–K+ ATPase activity in WKY cells, but decreases them in SHR cells. The effect of D3 receptor on D5 receptor expression and function was also confirmed in the D5 receptor-transfected HEK293 cells. It indicates that activation of D3 receptor increases D5 receptor expression and function. Altered regulation of D3 receptor on D5 receptors may have a role in the pathogenesis of hypertension.