D3 dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRs.
BACKGROUND
The dopaminergic and endothelin systems, by regulating sodium transport in the renal proximal tubule (RPT), participate in the control of blood pressure. The D(3) and ETB receptors are expressed in RPTs, and D(3) receptor function in RPTs is impaired in spontaneously hypertensive rats (SHRs). Therefore, we tested the hypothesis that D(3) receptors can regulate ETB receptors, and that D(3) receptor regulation of ETB receptors in RPTs is impaired in SHRs.


METHODS
ETB receptor expression in RPT cells was measured by immunoblotting and reverse transcriptase-PCR and ETB receptor function by measuring Na(+)-K(+) ATPase activity. D(3)/ETB receptor interaction was studied by co-immunoprecipitation.


RESULTS
In Wistar-Kyoto (WKY) RPT cells, the D(3) receptor agonist, PD128907, increased ETB receptor protein expression, effects that were blocked by removal of calcium in the culture medium. The stimulatory effect of D(3) on ETB receptor mRNA and protein expression was also blocked by nicardipine. In contrast, in SHR RPT cells, PD128907 decreased ETB receptor expression. Basal D(3)/ETB receptor co-immunoprecipitation was three times greater in WKY than in SHRs. The absolute amount of D(3)/ETB receptor co-immunoprecipitation induced by a D(3) receptor agonist was also greater in WKY than in SHRs. Stimulation of ETB receptors decreased Na(+)-K(+) ATPase activity in WKY but not in SHR cells. Pretreatment with PD128907 augmented the inhibitory effect of BQ3020 on Na(+)-K(+) ATPase activity in WKY but not in SHR cells.


CONCLUSIONS
D(3) receptors regulate ETB receptors by physical receptor interaction and govern receptor expression and function. D(3) receptor regulation of ETB receptors is aberrant in RPT cells from SHRs.
Yu
Changqing
C
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
Yang
Zhiwei
Z
Ren
Hongmei
H
Zhang
Yie
Y
Han
Yu
Y
He
Duofen
D
Lu
Quansheng
Q
Wang
Xiaoyan
X
Wang
Xukai
X
Yang
Chengming
C
Asico
Laureano D
LD
Hopfer
Ulrich
U
Eisner
Gilbert M
GM
Jose
Pedro A
PA
Zeng
Chunyu
C
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D047468:Immunoprecipitation; D007189:Indans / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044023:Receptor, Endothelin B / Q000235:genetics / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015290:Second Messenger Systems / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013045:Species Specificity
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007189:Indans; D010078:Oxazines; D044023:Receptor, Endothelin B; D050637:Receptors, Dopamine D3; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; D009529:Nicardipine; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase