title: Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells.
abstract: Angiotensin II type 1 (AT1) receptor and D1 and D3 dopamine receptors directly interact in renal proximal tubule (RPT) cells from normotensive Wistar-Kyoto rats (WKY). There is indirect evidence for a D5 and AT1 receptor interaction in WKY and spontaneously hypertensive rats (SHR). Therefore, we sought direct evidence of an interaction between AT1 and D5 receptors in RPT cells. D5 and AT1 receptors colocalized in WKY cells. Angiotensin II decreased D5 receptors in WKY cells in a time- and concentration-dependent manner (EC50=2.7x10(-9) M; t(1/2)=4.9 hours), effects that were blocked by an AT1 receptor antagonist (losartan). In SHR, angiotensin II (10(-8) M/24 hours) also decreased D5 receptors (0.96+/-0.08 versus 0.72+/-0.08; n=12) and to the same degree as in WKY cells (1.44+/-0.07 versus 0.92+/-0.08). However, basal D5 receptors were decreased in SHR RPT cells (SHR 0.96+/-0.08; WKY 1.44+/-0.07; n=12 per strain; P<0.05) and renal brush border membranes of SHR compared with WKY (SHR 0.54+/-0.16 versus WKY 1.46+/-0.10; n=5 per strain; P<0.05). Angiotensin II decreased AT1 receptor expression in WKY (1.00+/-0.04 versus 0.72+/-0.08; n=8; P<0.05) but increased it in SHR (0.96+/-0.04 versus 1.32+/-0.08; n=8; P<0.05). AT(1) and D5 receptors also interacted in vivo; renal D5 receptor protein was higher in mice lacking the AT1A receptor (AT1A-/-; 1.61+/-0.31; n=6) than in wild-type littermates used as controls (AT1A+/+; 0.81+/-0.08; n=6; P<0.05), and renal cortical AT1 receptor protein was higher in D5 receptor null mice than in wild-type littermates (1.18+/-0.08 versus 0.84+/-0.07; n=4; P<0.05). We conclude that D5 and AT1 receptors interact with each other. Altered interactions between AT1 and dopamine receptors may play a role in the pathogenesis of hypertension.
authors.affiliation: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, P.R. China. cyzeng1@hotmail.com
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Jones
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Joanna
authors.initials: J
authors.lastname: Altea
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Mangrum
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hopfer
authors.forename: David R
authors.initials: DR
authors.lastname: Sibley
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Eisner
authors.forename: Robin A
authors.initials: RA
authors.lastname: Felder
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D050641:Receptors, Dopamine D5; D014018:Tissue Distribution
chemical_list: C493606:Drd5 protein, mouse; C493607:Drd5 protein, rat; D044140:Receptor, Angiotensin, Type 1; D017447:Receptors, Dopamine D1; D000804:Angiotensin II; D050641:Receptors, Dopamine D5