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 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.
Dept. of Cardiology, Daping Hospital, The Third Military Medical Univ., Chongqing, P.R. China. chunyuzeng01@163.com.
Shaoxiong
S
Wang
Xi
X
Lu
Jian
J
Yang
Hongyong
H
Wang
CaiYu
C
Chen
Yu
Y
Han
Hongmei
H
Ren
Shuo
S
Zheng
Duofen
D
He
Lin
L
Zhou
Laureano D
LD
Asico
Wei Eric
WE
Wang
Pedro A
PA
Jose
Chunyu
C
Zeng
D000818:Animals; D002478:Cells, Cultured; D018818:Fenoldopam / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000819:agonists; D050641:Receptors, Dopamine D5 / Q000502:physiology*
D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D008995:Monoamine Oxidase; C521557:renalase; D011493:Protein Kinase C; D018818:Fenoldopam
dopamine receptor; hypertension; renal proximal tubule cells; renalase