Evidence map›Paper›PMID 23097213›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2013

Novel screening assay for the selective detection of G-protein-coupled receptor heteromer signaling.

Richard M van Rijn, Jessica H Harvey, Daniela I Brissett, Julia N DeFriel, Jennifer L Whistler

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

Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

8 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Functional histamine HPharmacological research · 2018
    Article
  6. Article
  7. Review
  8. Article
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

5 authors at 2 institutions in 1 country.

Richard M van RijnErnest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA. rvanrijn@gallo.ucsf.edu
Jessica H Harvey
Daniela I Brissett
Julia N DeFriel
Jennifer L Whistler
University of California, San Francisco · USErnest Gallo Clinic and Research Center · US

Funding

Vector, Transgenic, and Imaging CoreP50AA017072 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RON, DORIT · 2008 to 2017
$13.9M
Trafficking and signaling of opioid receptor subtypes and heterodimersR01DA015232 · NIDA · ERNEST GALLO CLINIC AND RESEARCH CENTER · PI WHISTLER, JENNIFER L · 2003 to 2010
$2.0M
Role of opioid receptor trafficking in tolerance and dependenceR01DA019958 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WHISTLER, JENNIFER L · 2007 to 2011
$1.8M
Selectively targeting delta opioid receptor subtypes to control drinking behaviorR01AA020401 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WHISTLER, JENNIFER L · 2011 to 2015
$1.8M
Development of a preclinical candidate for the treatment of alcoholismK99AA020539 · NIAAA · ERNEST GALLO CLINIC AND RESEARCH CENTER · PI VAN RIJN, RICHARD M. · 2011 to 2012
$178k
NIAAA NIH HHS K99 AA020539NIAAA NIH HHS K99AA020539NIAAA NIH HHS P50 AA017072NIAAA NIH HHS P50AA017072-03NIAAA NIH HHS R01 AA020401NIAAA NIH HHS R01AA020401NIDA NIH HHS R01 DA015232NIDA NIH HHS R01DA015232NIDA NIH HHS R01 DA019958NIDA NIH HHS R01DA019958
6 · The paper itself

Abstract

Drugs targeting G-protein-coupled receptors (GPCRs) make up more than 25% of all prescribed medicines. The ability of GPCRs to form heteromers with unique signaling properties suggests an entirely new and unexplored pool of drug targets. However, current in vitro assays are ill equipped to detect heteromer-selective compounds. We have successfully adapted an approach, using fusion proteins of GPCRs and chimeric G proteins, to create an in vitro screening assay (in human embryonic kidney cells) in which only activated heteromers are detectable. Here we show that this assay can demonstrate heteromer-selective G-protein bias as well as measure transinhibition. Using this assay, we reveal that the δ-opioid receptor agonist ADL5859, which is currently in clinical trials, has a 10-fold higher potency against δ-opioid receptor homomers than δ/μ-opioid receptor heteromers (pEC(50) = 6.7 ± 0.1 versus 5.8 ± 0.2). The assay enables the screening of large compound libraries to identify heteromer-selective compounds that could then be used in vivo to determine the functional role of heteromers and develop potential therapeutic agents.

Indexed as

Amino Acid SequenceBenzamidesCalciumCalcium SignalingCloning, MolecularDose-Response Relationship, DrugDrug Evaluation, PreclinicalEnkephalin, LeucineEnzyme-Linked Immunosorbent AssayGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein alpha Subunits, GsHEK293 CellsHumansMicroscopy, FluorescenceMolecular Sequence DataMutant Chimeric Proteins4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamideBenzamidesCalciumEnkephalin, LeucineGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein alpha Subunits, GsMutant Chimeric ProteinsPiperazinesReceptors, G-Protein-CoupledReceptors, Opioid, deltaRecombinant Fusion Proteins

Identifiers

PMID23097213
PMCPMC3533407
OpenAlexW2027341554

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.