Evidence map›Paper›PMID 27178731›Full record

ReviewPharmacological research2016

G protein-coupled receptor kinases as regulators of dopamine receptor functions.

Eugenia V Gurevich, Raul R Gainetdinov, Vsevolod V Gurevich

Abstract readReview
In one paragraph

Review in Pharmacological research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 3 pooled it
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 3 syntheses or guidelines pooled it, 135 citations in OpenAlex.

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  17. Pharmaceuticals (Basel, Switzerland) · 2025
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21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Eugenia V GurevichDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37221, USA. Electronic address: Eugenia.Gurevich@vanderbilt.edu.
Raul R GainetdinovInstitute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, 199034, Russia; Skolkovo Institute of Science and Technology, Skolkovo, 143025, Moscow, Russia.
Vsevolod V GurevichDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37221, USA.
Vanderbilt University · USSkolkovo Institute of Science and Technology · RU

Funding

STRUCTURE/FUNCTION STUDIES OF VISUAL ARRESTINR01EY011500 · NEI · VANDERBILT UNIVERSITY · PI T M Iverson · 1997 to 2026
$12.3M
Arrestin interactions with non-receptor binding partnersR01GM077561 · NIGMS · VANDERBILT UNIVERSITY · PI GUREVICH, VSEVOLOD V. · 2007 to 2015
$2.3M
Signaling regulation in the striatum in Parkinson's diseaseR01NS065868 · NINDS · VANDERBILT UNIVERSITY · PI GUREVICH, EUGENIA V · 2009 to 2013
$1.7M
Conformational regulation of arrestin-mediated signalingR01GM081756 · NIGMS · VANDERBILT UNIVERSITY · PI GUREVICH, VSEVOLOD V. · 2008 to 2011
$1.5M
Regulation of GPCR signaling with receptor-specific arrestinsR01GM109955 · NIGMS · VANDERBILT UNIVERSITY · PI GUREVICH, VSEVOLOD V. · 2015 to 2017
$1.1M
The role of receptor desensitization machinery in psychostimulant addictionR21DA030103 · NIDA · VANDERBILT UNIVERSITY · PI GUREVICH, EUGENIA V · 2011 to 2012
$390k
NEI NIH HHS R01 EY011500NIDA NIH HHS R21 DA030103NIGMS NIH HHS R01 GM077561NIGMS NIH HHS R01 GM081756NIGMS NIH HHS R01 GM109955NINDS NIH HHS R01 NS065868
6 · The paper itself

Abstract

Actions of the neurotransmitter dopamine in the brain are mediated by dopamine receptors that belong to the superfamily of G protein-coupled receptors (GPCRs). Mammals have five dopamine receptor subtypes, D1 through D5. D1 and D5 couple to Gs/olf and activate adenylyl cyclase, whereas D2, D3, and D4 couple to Gi/o and inhibit it. Most GPCRs upon activation by an agonist are phosphorylated by GPCR kinases (GRKs). The GRK phosphorylation makes receptors high-affinity binding partners for arrestin proteins. Arrestin binding to active phosphorylated receptors stops further G protein activation and promotes receptor internalization, recycling or degradation, thereby regulating their signaling and trafficking. Four non- visual GRKs are expressed in striatal neurons. Here we describe known effects of individual GRKs on dopamine receptors in cell culture and in the two in vivo models of dopamine-mediated signaling: behavioral response to psychostimulants and L-DOPA- induced dyskinesia. Dyskinesia, associated with dopamine super-sensitivity of striatal neurons, is a debilitating side effect of L-DOPA therapy in Parkinson's disease. In vivo, GRK subtypes show greater receptor specificity than in vitro or in cultured cells. Overexpression, knockdown, and knockout of individual GRKs, particularly GRK2 and GRK6, have differential effects on signaling of dopamine receptor subtypes in the brain. Furthermore, deletion of GRK isoforms in select striatal neuronal types differentially affects psychostimulant-induced behaviors. In addition, anti-dyskinetic effect of GRK3 does not require its kinase activity: it is mediated by the binding of its RGS-like domain to Gαq/11, which suppresses Gq/11 signaling. The data demonstrate that the dopamine signaling in defined neuronal types in vivo is regulated by specific and finely orchestrated actions of GRK isoforms.

Indexed as

Signal TransductionAnimalsBasal GangliaCentral Nervous System StimulantsG-Protein-Coupled Receptor KinasesHumansParkinsonian DisordersPhosphorylationReceptors, DopamineCentral Nervous System StimulantsG-Protein-Coupled Receptor KinasesReceptors, DopamineDopamine receptorDyskinesiaG protein-coupled receptor kinaseL-DOPAParkinson’s diseasePsychostimulants

Identifiers

PMID27178731
PMCPMC5079267
OpenAlexW2383568686

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.