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Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. 2005

Chunyu Zeng, and Zhiwei Yang, and Zheng Wang, and John Jones, and Xiaoyan Wang, and Joanna Altea, and Amy J Mangrum, and Ulrich Hopfer, and David R Sibley, and Gilbert M Eisner, and Robin A Felder, and Pedro A Jose
Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, P.R. China. cyzeng1@hotmail.com

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.

UI MeSH Term Description Entries
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D011921 Rats, Inbred WKY A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR). Rats, Wistar Kyoto,Wistar Kyoto Rat,Rats, WKY,Inbred WKY Rat,Inbred WKY Rats,Kyoto Rat, Wistar,Rat, Inbred WKY,Rat, WKY,Rat, Wistar Kyoto,WKY Rat,WKY Rat, Inbred,WKY Rats,WKY Rats, Inbred,Wistar Kyoto Rats
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D017447 Receptors, Dopamine D1 A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES. Dopamine D1 Receptors,Dopamine-D1 Receptor,D1 Receptors, Dopamine,Dopamine D1 Receptor,Receptor, Dopamine-D1

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