title: Enhanced Natriuresis and Diuresis in Wistar Rats Caused by the Costimulation of Renal Dopamine D3 and Angiotensin II Type 2 Receptors.
abstract: BACKGROUND
  The kidney, via its regulation of sodium excretion, which is modulated by humoral factors, including the dopamine and renin-angiotensin systems, keeps the blood pressure in the normal range. We have reported a negative interaction between dopamine D3 and AT1 receptors (D3R and AT1R) in renal proximal tubule (RPT) cells. Here, we studied the interaction between D3R and AT2R in vitro and in vivo.
  
  
  RESULTS
  Stimulation of either the D3R or AT2R, by the intrarenal arterial infusion of PD128907, a D3R agonist, or CGP42112A, an AT2R agonist, induced natriuresis and diuresis that were enhanced by the simultaneous infusion of PD128907 and CGP42112A in Wistar rats. The D3/AT2 receptor interaction was confirmed in in vitro, i.e., stimulation of either the D3R or AT2R inhibited Na(+)-K(+)-ATPase activity that was enhanced by the costimulation of these receptors. D3R and AT2R colocalized and coimmunoprecipitated in kidney and RPT cells (RPTCs). Stimulation of one receptor increased the localization of the other receptor at the plasma cell membrane. ERK1/2-MAPK is involved in the signaling pathway of D3R and AT2R interaction because costimulation of D3R and AT2R significantly increased ERK1/2-MAPK expression in RPTCs; inhibition of ERK1/2-MAPK abolished the inhibition of Na(+)-K(+)-ATPase activity that was enhanced by D3R and AT2R costimulation.
  
  
  CONCLUSIONS
  Our current study indicates that D3R, in combination with AT2R, enhances natriuresis and diuresis, via ERK1/2-MAPK pathway, that may be involved in the regulation of blood pressure.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China; Chongqing Institute of Cardiology, Chongqing, China;
authors.forename: Sufei
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China; Chongqing Institute of Cardiology, Chongqing, China;
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China; Chongqing Institute of Cardiology, Chongqing, China;
authors.forename: Shuo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China; Chongqing Institute of Cardiology, Chongqing, China;
authors.forename: Xun
authors.initials: X
authors.lastname: Kou
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA;
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China; Chongqing Institute of Cardiology, Chongqing, China;
authors.forename: Hefei
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China; Chongqing Institute of Cardiology, Chongqing, China;
authors.forename: Zhao
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China; Chongqing Institute of Cardiology, Chongqing, China; chunyuzeng01@163.com.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009318:Natriuresis; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D044139:Receptor, Angiotensin, Type 2; D050638:Receptors, Dopamine D4; D000254:Sodium-Potassium-Exchanging ATPase
keywords: angiotensin II type 2 receptor; blood pressure; dopamine D3 receptor; hypertension; kidney; kidney tubules; proximal.