Abstract 503: Regulation of D5 Dopamine Receptor on Renalase Expression and Function in Rat Renal Proximal Tubule Cells

Abstract

The dopaminergic and sympathetic systems interact to regulate blood pressure. Our previous studies show the regulation of dopamine receptor on α 1 -adrenergic receptor function. Due to the regulation of renalase on sympathetic tone, we hypothesize that dopamine receptor, especially D 1 -like receptor, might regulate renalase in kidney. The effect of D 1 -like receptor on renalase expression and function was checked in immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). It resulted that D 1 -like receptor agonist, fenoldopam (10 -7 -10 -5 M), increased renalase protein expression and function in WKY RPT cells, in contrast, decreased it in SHR cells. These effects were blocked by D 1 -like receptor antagonist SCH 23390 (10 -6 M). Fenoldopam increased renalase mRNA level in WKY RPT cells, but not in SHR cells. Fenoldopam increased the degradation of renalase protein in both WKY and SHR cells. However, the degradation degree was higher in SHR cells than in WKY cells. The regulation of D 1 -like receptor on renalase was mainly via D 5 receptor, because inhibition of D 5 , not D 1 receptor, by antisense blocked inhibitory effect of D 1 -like receptor on renalase in WKY cells. Moreover, inhibition of PKC, by PKC inhibitor 19-31, blocked the effect of fenoldopam on renalase expression; stimulation of PKC, by PKC agonist (PMA), inhibited renalase expression and function, indicating that PKC is involved in the process. Consistent with the in-vitro study, renalase expression was lower in kidney from SHRs than in WKY rats. It indicated that D 1 -like receptor, via D 5 receptor, regulates renalase expression and function in RPT cells, aberrant regulation of D 5 receptor on renalase might be involved in the pathogenesis of hypertension.