title: Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR.
abstract: Dopamine and angiotensin II negatively interact to regulate sodium excretion and blood pressure. D3 dopamine receptors downregulate angiotensin type 1 (AT1) receptors in renal proximal tubule cells from normotensive Wistar-Kyoto rats. We determined whether AT1 receptors regulate D3 receptors and whether the regulation is different in cultured renal proximal tubule cells from normotensive and spontaneously hypertensive rats. Angiotensin II (10(-8)M/24 hours) decreased D3 receptors in both normotensive (control, 36+/-3; angiotensin II, 24+/-3 U) and hypertensive (control, 30+/-3; angiotensin II, 11+/-3 U; n=9 per group) rats; effects that were blocked by the AT1 receptor antagonist, losartan (10(-8)M/24 hours). However, the reduction in D3 expression was greater in hypertensive (60+/-10%) than in normotensive rats (32+/-9%). In normotensive rats, angiotensin II (10(-8)M/24hr) also decreased AT1 receptors. In contrast, in cells from hypertensive rats, angiotensin II increased AT1 receptors. AT1 and D3 receptors co-immunoprecipitated in renal proximal tubule cells from both strains. Angiotensin II decreased D3/AT1 receptor co-immunoprecipitation similarly in both rat strains, but basal D3/AT1 co-immunoprecipitation was 6 times higher in normotensive than in hypertensive rats. Therefore, AT1 and D3 receptor interaction is qualitatively and quantitatively different between normotensive and hypertensive rats; angiotensin II decreases AT1 expression in normotensive but increases it in hypertensive rats. In addition, angiotensin II decreases D3 expression to a greater extent in hypertensive than in normotensive rats. Aberrant interactions between D3 and AT1 receptors may play a role in the pathogenesis of hypertension.
authors.affiliation: Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA. cyzeng1@hotmail.com
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hopfer
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; D000918:Antibody Specificity; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism*; D015151:Immunoblotting; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000276:immunology / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000276:immunology / Q000378:metabolism*; D050637:Receptors, Dopamine D3
chemical_list: C493595:Drd3 protein, rat; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000804:Angiotensin II