D3 dopamine receptor regulation of D5 receptor expression and function in renal proximal tubule cells.
Dopamine receptor, via D(1)-like and D(2)-like receptors, increases sodium excretion in kidney. We have reported positive interactions between D(3) and D(1) receptors in renal proximal tubule (RPT) cells. These reports, however do not preclude that there may be also interaction between D(3) and D(5) receptors, because of the lack of selective D(1) and D(5) receptor agonists or antagonists. We hypothesize that D(3) receptors can regulate D(5) receptors, and that D(3) receptor regulation of D(5) receptors in RPTs is impaired in spontaneously hypertensive rats (SHRs). It showed that a D(3) receptor agonist, PD128907, by the activation of protein kinase C activity, increased the expression of D(5) receptors in a concentration- and time-dependent manner in RPT cells from Wistar-Kyoto (WKY) rats. The stimulatory effect of the D(3) receptor on D(5) receptor expression was impaired in RPT cells from SHRs. The effect of D(3) receptor on D(5) receptor is functionally relevant; stimulation of D(5) receptor decreases Na(+)-K(+) adenosine triphosphatase (ATPase) activity in WKY cells. Pretreatment with D(3) receptor agonist for 24 h enhances the D(5) receptor expression and D(5) receptor-mediated inhibitory effect on Na(+)-K(+) ATPase activity in WKY cells, but decreases them in SHR cells. The effect of D(3) receptor on D(5) receptor expression and function was also confirmed in the D(5) receptor-transfected HEK293 cells. It indicates that activation of D(3) receptor increases D(5) receptor expression and function. Altered regulation of D(3) receptor on D(5) receptors may have a role in the pathogenesis of hypertension.
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, PR China.
Hefei
H
Huang
Hongmei
H
Ren
Caiyu
C
Chen
Xiaoyan
X
Wang
Jian
J
Yang
Yu
Y
Han
Duofen
D
He
Lin
L
Zhou
Laureano D
LD
Asico
Pedro A
PA
Jose
Chunyu
C
Zeng
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010078:Oxazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D050641:Receptors, Dopamine D5 / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D001578:Benzopyrans; D010078:Oxazines; D050637:Receptors, Dopamine D3; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D050641:Receptors, Dopamine D5; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase