Regulation of renalase expression by D5 dopamine receptors in rat renal proximal tubule cells

The dopaminergic and sympathetic systems interact to regulate blood pressure. Our previous studies showed regulation of alpha(1)-adrenergic receptor function by D-1-like dopamine receptors in vascular smooth muscle cells. Because renalase could regulate circulating epinephrine levels and dopamine production in renal proximal tubules (RPTs), we tested the hypothesis that D-1-like receptors regulate renalase expression in kidney. The effect of D-1-like receptor stimulation on renalase expression and function was measured in immortalized RPT cells from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). We found that the D-1-like receptor agonist fenoldopam (10(-7)-10(-5) mol/l) increased renalase protein expression and function in WKY RPT cells but decreased them in SHR cells. Fenoldopam also increased renalase mRNA levels in WKY but not in SHR cells. In contrast, fenoldopam increased the degradation of renalase protein in SHR cells but not in WKY cells. The regulation of renalase by the D-1-like receptor was mainly via the D-5 receptor because silencing of the D5 but not D-1 receptor by antisense oligonucleotides blocked the stimulatory effect of the D-1-like receptor on renalase expression in WKY cells. Moreover, inhibition of PKC, by the PKC inhibitor 19-31, blocked the stimulatory effect of fenoldopam on renalase expression while stimulation of PKC, by a PKC agonist (PMA), increased renalase expression, indicating that PKC is involved in the process. Our studies suggest that the D-5 receptor positively regulates renalase expression in WKY but not SHR RPT cells; aberrant regulation of renalase by the D-5 receptor may be involved in the pathogenesis of hypertension.