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

Authors

Shaoxiong Wang, Daping Hospital, the Third Military Medical University
Xi Lu, Daping Hospital, the Third Military Medical University
Jian Yang, Daping Hospital, the Third Military Medical University
Hongyong Wang, Daping Hospital, the Third Military Medical University
Cai Yu Chen, Daping Hospital, the Third Military Medical University
Yu Han, Daping Hospital, the Third Military Medical University
Hongmei Ren, Daping Hospital, the Third Military Medical University
Shuo Zheng, Daping Hospital, the Third Military Medical University
Duofen He, Daping Hospital, the Third Military Medical University
Lin Zhou, Daping Hospital, the Third Military Medical University
Laureano D. Asico, University of Maryland School of Medicine
Wei Eric Wang, Daping Hospital, the Third Military Medical University
Pedro A. Jose, University of Maryland School of Medicine
Chunyu Zeng, Daping Hospital, the Third Military Medical University

Document Type

Journal Article

Publication Date

3-15-2014

Journal

American Journal of Physiology - Renal Physiology

Volume

306

Issue

6

DOI

10.1152/ajprenal.00196.2013

Keywords

Dopamine receptor; Hypertension; Renal proximal tubule cells; Renalase

Abstract

The dopaminergic and sympathetic systems interact to regulate blood pressure. Our previous studies showed regulation of α1-adrenergic receptor function by D1-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 D1-like receptors regulate renalase expression in kidney. The effect of D1-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 D1-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 D1-like receptor was mainly via the D5 receptor because silencing of the D5 but not D1 receptor by antisense oligonucleotides blocked the stimulatory effect of the D1-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 D5 receptor positively regulates renalase expression in WKY but not SHR RPT cells; aberrant regulation of renalase by the D5 receptor may be involved in the pathogenesis of hypertension. © 2014 the American Physiological Society.

APA Citation

Wang, S., Lu, X., Yang, J., Wang, H., Chen, C., Han, Y., Ren, H., Zheng, S., He, D., Zhou, L., Asico, L., Wang, W., Jose, P., & Zeng, C. (2014). Regulation of renalase expression by D₅ dopamine receptors in rat renal proximal tubule cells. American Journal of Physiology - Renal Physiology, 306 (6). http://dx.doi.org/10.1152/ajprenal.00196.2013