Evidence map›Paper›PMID 25245406›Full record

ArticleMolecular pharmacology2014

Glycine and GABA(A) ultra-sensitive ethanol receptors as novel tools for alcohol and brain research.

Anna Naito, Karan H Muchhala, Liana Asatryan, James R Trudell, Gregg E Homanics, Daya I Perkins, Daryl L Davies, Ronald L Alkana

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 35% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
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  3. Review
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  5. Article
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  7. A newly developed anesthetic based on a unique chemical core.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
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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

8 authors at 1 institution in 1 country.

Anna NaitoDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.).
Karan H MuchhalaDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.).
Liana AsatryanDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.).
James R TrudellDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.).
Gregg E HomanicsDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.).ORCID http://orcid.org/0000-0003-3641-8153
Daya I PerkinsDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.).
Daryl L DaviesDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.) ddavies@usc.edu.
Ronald L AlkanaDepartment of Pharmacology and Pharmaceutical Sciences (A.N., K.H.M., R.L.A.) and Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and Policy (L.A., D.L.D.), University of Southern California School of Pharmacy, Los Angeles, California; Department of Anesthesia, Beckman Program for Molecular and Genetic Medicine, Stanford University, Stanford University Medical Center, Stanford, California (J.R.T.); Departments of Anesthesiology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.E.H.); and Amgen Inc., Thousand Oaks, California (D.I.P.).
University of Southern California · US

Funding

Regulation of Alcohol Intake by Purinergic P2X4 ReceptorsR01AA022448 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DAVIES, DARYL L · 2013 to 2020
$2.9M
Dissemination of a MI-Based Preparatory ProcedureR01AA013992 · NIAAA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI WALITZER, KIMBERLY S. · 2004 to 2008
$2.8M
Properties of Specific Alcohol Binding SitesR01AA013378 · NIAAA · STANFORD UNIVERSITY · PI TRUDELL, JAMES ROBERT · 2002 to 2009
$1.9M
Defining Alcohol Binding Sites in Ligand-Gated Ion ChannelsR01AA020980 · NIAAA · STANFORD UNIVERSITY · PI BERTACCINI, EDWARD J · 2013 to 2017
$1.6M
Sites of Ethanol Action in Purinergic P2X4 ReceptorsK01AA017243 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ASATRYAN, LIANA · 2008 to 2011
$484k
NIAAA NIH HHS K01 AA017243NIAAA NIH HHS K01-AA17243NIAAA NIH HHS R01 AA013378NIAAA NIH HHS R01 AA013992NIAAA NIH HHS R01 AA020980NIAAA NIH HHS R01 AA022448NIAAA NIH HHS R01-AA022448NIAAA NIH HHS R01-AA13378NIAAA NIH HHS R01-AA13992
6 · The paper itself

Abstract

A critical obstacle to developing effective medications to prevent and/or treat alcohol use disorders is the lack of specific knowledge regarding the plethora of molecular targets and mechanisms underlying alcohol (ethanol) action in the brain. To identify the role of individual receptor subunits in ethanol-induced behaviors, we developed a novel class of ultra-sensitive ethanol receptors (USERs) that allow activation of a single receptor subunit population sensitized to extremely low ethanol concentrations. USERs were created by mutating as few as four residues in the extracellular loop 2 region of glycine receptors (GlyRs) or γ-aminobutyric acid type A receptors (GABA(A)Rs), which are implicated in causing many behavioral effects linked to ethanol abuse. USERs, expressed in Xenopus oocytes and tested using two-electrode voltage clamp, demonstrated an increase in ethanol sensitivity of 100-fold over wild-type receptors by significantly decreasing the threshold and increasing the magnitude of ethanol response, without altering general receptor properties including sensitivity to the neurosteroid, allopregnanolone. These profound changes in ethanol sensitivity were observed across multiple subunits of GlyRs and GABA(A)Rs. Collectively, our studies set the stage for using USER technology in genetically engineered animals as a unique tool to increase understanding of the neurobiological basis of the behavioral effects of ethanol.

Indexed as

AnimalsBrainEthanolFemalegamma-Aminobutyric AcidModels, MolecularPregnanoloneReceptors, GABA-AReceptors, GlycineStructure-Activity RelationshipXenopus laevisEthanolgamma-Aminobutyric AcidPregnanoloneReceptors, GABA-AReceptors, Glycine

Identifiers

PMID25245406
PMCPMC4244596
OpenAlexW2313954272

What OpenQuestion holds

Textmetadata
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.