title: Impaired stimulatory effect of ETB receptor on D₃ receptor in immortalized renal proximal tubule cells of spontaneously hypertensive rats.
abstract: BACKGROUND
  Activation of renal D₃ receptor induces natriuresis and diuresis in Wistar-Kyoto (WKY) rats; in the presence of ETB receptor antagonist, the natriuretic effect of D₃ receptor in WKY rats is reduced. We hypothesize that ETB receptor activation may regulate D₃ receptor expression in renal proximal tubule (RPT) cells from WKY rats, which is impaired in RPT cells from spontaneously hypertensive rats (SHRs).
  
  
  METHODS
  D₃ receptor expression was determined by immunoblotting; the D₃/ETB receptor linkage was checked by coimmunoprecipitation; Na(+)-K(+)-ATPase activity was determined as the rate of inorganic phosphate released in the presence or absence of ouabain.
  
  
  RESULTS
  In RPT cells from WKY rats, the ETB receptor agonist BQ3020 increased D₃ receptor protein. In contrast, in RPT cells from SHRs, BQ3020 did not increase D₃ receptor. There was coimmunoprecipitation between D₃ and ETB receptors in RPT cells from WKY and SHRs. Activation of ETB receptor increased D₃/ETB coimmunoprecipitation in RPT cells from WKY rats, but not from SHRs. The basal levels of D₃/ETB receptor coimmunoprecipitation were greater in RPT cells from WKY rats than in those from SHRs. Stimulation of D₃ receptor inhibited Na(+)-K(+)-ATPase activity, which was augmented by the pretreatment with the ETB receptor agonist BQ3020 in WKY RPT cells, but not in SHR RPT cells.
  
  
  CONCLUSIONS
  ETB receptors regulate and physically interact with D₃ receptors differently in WKY rats and SHRs. The impaired natriuretic effect in SHRs may be, in part, related to impaired ETB and D₃ receptor interactions.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Fu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Xukai
authors.initials: X
authors.lastname: Wang
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002460:Cell Line; D006973:Hypertension / Q000378:metabolism*; D047468:Immunoprecipitation; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044023:Receptor, Endothelin B / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: C493595:Drd3 protein, rat; D044023:Receptor, Endothelin B; D050637:Receptors, Dopamine D3; D000254:Sodium-Potassium-Exchanging ATPase