title: D3 dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRs.
abstract: 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.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Yu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.forename: Yie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Lu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Xukai
authors.initials: X
authors.lastname: Wang
authors.forename: Chengming
authors.initials: C
authors.lastname: Yang
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hopfer
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Eisner
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: 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
chemical_list: 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