| Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. | |
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MedLine Citation:
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PMID: 20153824 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Complex interactions between genes and environment result in a sodium-induced elevation in blood pressure (salt sensitivity) and/or hypertension that lead to significant morbidity and mortality affecting up to 25% of the middle-aged adult population worldwide. Determining the etiology of genetic and/or environmentally-induced high blood pressure has been difficult because of the many interacting systems involved. Two main pathways have been implicated as principal determinants of blood pressure since they are located in the kidney (the key organ responsible for blood pressure regulation), and have profound effects on sodium balance: the dopaminergic and renin-angiotensin systems. These systems counteract or modulate each other, in concert with a host of intracellular second messenger pathways to regulate sodium and water balance. In particular, the G protein-coupled receptor kinase type 4 (GRK4) appears to play a key role in regulating dopaminergic-mediated natriuresis. Constitutively activated GRK4 gene variants (R65L, A142V, and A486V), by themselves or by their interaction with other genes involved in blood pressure regulation, are associated with essential hypertension and/or salt-sensitive hypertension in several ethnic groups. GRK4γ 142Vtransgenic mice are hypertensive on normal salt intake while GRK4γ 486V transgenic mice develop hypertension only with an increase in salt intake. GRK4 gene variants have been shown to hyperphosphorylate, desensitize, and internalize two members of the dopamine receptor family, the D(1) (D(1)R) and D(3) (D(3)R) dopamine receptors, but also increase the expression of a key receptor of the renin-angiotensin system, the angiotensin type 1 receptor (AT(1)R). Knowledge of the numerous blood pressure regulatory pathways involving angiotensin and dopamine may provide new therapeutic approaches to the pharmacological regulation of sodium excretion and ultimately blood pressure control. |
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Authors:
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Pedro A Jose; Patricio Soares-da-Silva; Gilbert M Eisner; Robin A Felder |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review Date: 2010-02-12 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1802 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-12-21 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1259-67 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Children's National Medical Center, George Washington University for the Health Sciences, Washington, DC, USA. pjose@cnmc.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Amino Acid Substitution Animals Blood Pressure* Dopamine / genetics, metabolism* Female G-Protein-Coupled Receptor Kinase 4 / genetics, metabolism* Humans Hypertension / drug therapy, genetics, metabolism* Kidney / metabolism* Male Mice Mice, Transgenic Middle Aged Mutation, Missense Phosphorylation Receptor, Angiotensin, Type 1 / genetics, metabolism Receptors, Dopamine D1 / genetics, metabolism Receptors, Dopamine D3 / genetics, metabolism Renin-Angiotensin System / genetics |
| Grant Support | |
ID/Acronym/Agency:
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P01 HL068686-060004/HL/NHLBI NIH HHS; P01 HL074940-050003/HL/NHLBI NIH HHS; P01HL068686/HL/NHLBI NIH HHS; P01HL074940/HL/NHLBI NIH HHS; P50 DK052612-050003/DK/NIDDK NIH HHS; R01 DK039308-20/DK/NIDDK NIH HHS; R01 HL092196-01A1/HL/NHLBI NIH HHS; R01DK039308/DK/NIDDK NIH HHS; R01HL092196/HL/NHLBI NIH HHS; R37 HL023081-29/HL/NHLBI NIH HHS; R37HL023081/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptor, Angiotensin, Type 1; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D3; EC 2.7.11.16/G-Protein-Coupled Receptor Kinase 4; EC 2.7.11.16/GRK4 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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