Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells.
The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D(3) dopamine receptor gene in mice produces renin-dependent hypertension. In rats, D(2)-like receptors reduce angiotensin II binding sites in renal proximal tubules (RPTs). Because the major D(2)-like receptor in RPTs is the D(3) receptor, we examined whether D(3) receptors regulate angiotensin II type 1 (AT(1)) receptors in rat RPT cells. The effect of D(3) receptors on AT(1) receptors was studied in vitro and in vivo. The D(3) receptor agonist PD128907 decreased AT(1) receptor protein and mRNA in WKY RPT cells and increased it in SHR cells. PD128907 increased D(3) receptors in WKY cells but had no effect in SHR cells. D(3)/AT(1) receptors colocalized in RPT cells; D(3) receptor stimulation decreased the percent amount of D(3) receptors that coimmunoprecipitated with AT(1) receptors to a greater extent in WKY than in SHR cells. However, D(3) receptor stimulation did not change the percent amount of AT(1) receptors that coimmunoprecipitated with D(3) receptors in WKY cells and markedly decreased the coimmunoprecipitation in SHR cells. The D(3) receptor also regulated the AT(1) receptor in vivo because AT(1) receptor expression was increased in kidneys of D(3) receptor-null mice compared with wild type littermates. D(3) receptors may regulate AT(1) receptor function by direct interaction with and regulation of AT(1) receptor expression. One mechanism of hypertension may be related to increased renal expression of AT(1) receptors due decreased D(3) receptor regulation.
Zeng
Chunyu
C
Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China. cyzeng1@hotmail.com
Liu
Yan
Y
Wang
Zheng
Z
He
Duofen
D
Huang
Lan
L
Yu
Peiying
P
Zheng
Shaopeng
S
Jones
John E
JE
Asico
Laureano D
LD
Hopfer
Ulrich
U
Eisner
Gilbert M
GM
Felder
Robin A
RA
Jose
Pedro A
PA
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000172:deficiency / Q000378:metabolism*; D014018:Tissue Distribution
D047228:Angiotensin II Type 1 Receptor Blockers; D001578:Benzopyrans; D018491:Dopamine Agonists; D010078:Oxazines; D044140:Receptor, Angiotensin, Type 1; D050637:Receptors, Dopamine D3; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol