ArticleAmerican journal of physiology. Heart and circulatory physiology2008
Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction.
Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 48 citations in OpenAlex.
- G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.Pharmacology & therapeutics · 2022Review
- Loss of dynamic regulation of G protein-coupled receptor kinase 2 by nitric oxide leads to cardiovascular dysfunction with aging.American journal of physiology. Heart and circulatory physiology · 2020Article
- Chronic Elevation of Endothelin-1 Alone May Not Be Sufficient to Impair Endothelium-Dependent Relaxation.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Small-Molecule G Protein-Coupled Receptor Kinase Inhibitors Attenuate G Protein-Coupled Receptor Kinase 2-Mediated Desensitization of Vasoconstrictor-Induced Arterial Contractions.Molecular pharmacology · 2018Article
- G Protein-Coupled Receptor Kinases: Crucial Regulators of Blood Pressure.Journal of the American Heart Association · 2016Review
- Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor desensitization in hypertension.American journal of physiology. Cell physiology · 2015Article
- GRK2 targeted knock-down results in spontaneous hypertension, and altered vascular GPCR signaling.The Journal of biological chemistry · 2015Article
- Melanopsin mediates light-dependent relaxation in blood vessels.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Exploiting functional domains of GRK2/3 to alter the competitive balance of pro- and anticontractile signaling in airway smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2.The Journal of clinical investigation · 2013Article
- G-protein-coupled receptor kinase 2 and hypertension: molecular insights and pathophysiological mechanisms.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2013Review
- Molecular mechanism for inhibition of g protein-coupled receptor kinase 2 by a selective RNA aptamer.Structure (London, England : 1993) · 2012Article
- G protein-coupled receptor kinases: more than just kinases and not only for GPCRs.Pharmacology & therapeutics · 2012Review
- Taking the heart failure battle inside the cell: small molecule targeting of Gβγ subunits.Journal of molecular and cellular cardiology · 2011Review
- G protein coupled receptor kinases as therapeutic targets in cardiovascular disease.Circulation research · 2011Review
- G protein-coupled receptor kinase 2 and arrestin2 regulate arterial smooth muscle P2Y-purinoceptor signalling.Cardiovascular research · 2011Article
- The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets.British journal of pharmacology · 2010Review
- Endothelin signalling in arterial smooth muscle is tightly regulated by G protein-coupled receptor kinase 2.Cardiovascular research · 2010Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptor kinase 2 (GRK2) is a serine/theorinine kinase that phosphorylates and desensitizes agonist-bound G protein-coupled receptors. GRK2 is increased in expression and activity in lymphocytes and vascular smooth muscle (VSM) in human hypertension and animal models of the disease. Inhibition of GRK2 using the carboxyl-terminal portion of the protein (GRK2ct) has been an effective tool to restore compromised beta-adrenergic receptor (AR) function in heart failure and improve outcome. A well-characterized dysfunction in hypertension is attenuation of betaAR-mediated vasodilation. Therefore, we tested the role of inhibition of GRK2 using GRK2ct or VSM-selective GRK2 gene ablation in a renal artery stenosis model of elevated blood pressure (BP) [the two-kidney, one-clip (2K1C) model]. Use of the 2K1C model resulted in a 30% increase in conscious BP, a threefold increase in plasma norepinephrine levels, and a 50% increase in VSM GRK2 mRNA levels. BP remained increased despite VSM-specific GRK2 inhibition by either GRK2 knockout (GRK2KO) or peptide inhibition (GRK2ct). Although betaAR-mediated dilation in vivo and in situ was enhanced, alpha(1)AR-mediated vasoconstriction was also increased. Further pharmacological experiments using alpha(1)AR antagonists revealed that GRK2 inhibition of expression (GRK2KO) or activity (GRK2ct) enhanced alpha(1D)AR vasoconstriction. This is the first study to suggest that VSM alpha(1D)ARs are a GRK2 substrate in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.