Evidence map›Paper›PMID 22665477›Full record

ArticleThe Journal of biological chemistry2012

Function of human α3β4α5 nicotinic acetylcholine receptors is reduced by the α5(D398N) variant.

Andrew A George, Linda M Lucero, M Imad Damaj, Ronald J Lukas, Xiangning Chen, Paul Whiteaker

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

36 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Article
  3. Analogs of α-conotoxin PnIC selectively inhibit α7β2- over α7-only subtype nicotinic acetylcholine receptors via a novel allosteric mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Little Evidence of Modified Genetic Effect of rs16969968 on Heavy Smoking Based on Age of Onset of Smoking.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2021
    Article
  9. Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors.Cellular and molecular life sciences : CMLS · 2021
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Chrna5-Expressing Neurons in the Interpeduncular Nucleus Mediate Aversion Primed by Prior Stimulation or Nicotine Exposure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Article
  18. Review
  19. Review
  20. Isoform-specific mechanisms of α3β4*-nicotinic acetylcholine receptor modulation by the prototoxin lynx1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    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

6 authors at 2 institutions in 1 country.

Andrew A GeorgeDivision of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona 85013, USA.
Linda M Lucero
M Imad Damaj
Ronald J Lukas
Xiangning Chen
Paul Whiteaker
Barrow Neurological Institute · USVirginia Commonwealth University · US

Funding

Variants in CHRNA5/CHRNA3/CHRNB4 and nicotine dependenceR21DA027070 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI CHEN, XIANGNING · 2009 to 2010
$897k
Construction and Expression of Concatemeric alpha6beta2* Nicotinic Acetycholine RR21DA026627 · NIDA · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · PI WHITEAKER, PAUL · 2009 to 2010
$407k
NIDA NIH HHS R21 DA026627NIDA NIH HHS R21 DA027070NIDA NIH HHS R21 DA027070-02S1
6 · The paper itself

Abstract

Genome-wide studies have strongly associated a non-synonymous polymorphism (rs16969968) that changes the 398th amino acid in the nAChR α5 subunit from aspartic acid to asparagine (D398N), with greater risk for increased nicotine consumption. We have used a pentameric concatemer approach to express defined and consistent populations of α3β4α5 nAChR in Xenopus oocytes. α5(Asn-398; risk) variant incorporation reduces ACh-evoked function compared with inclusion of the common α5(Asp-398) variant without altering agonist or antagonist potencies. Unlinked α3, β4, and α5 subunits assemble to form a uniform nAChR population with pharmacological properties matching those of concatemeric α3β4* nAChRs. α5 subunit incorporation reduces α3β4* nAChR function after coinjection with unlinked α3 and β4 subunits but increases that of α3β4α5 versus α3β4-only concatemers. α5 subunit incorporation into α3β4* nAChR also alters the relative efficacies of competitive agonists and changes the potency of the non-competitive antagonist mecamylamine. Additional observations indicated that in the absence of α5 subunits, free α3 and β4 subunits form at least two further subtypes. The pharmacological profiles of these free subunit α3β4-only subtypes are dissimilar both to each other and to those of α3β4α5 nAChR. The α5 variant-induced change in α3β4α5 nAChR function may underlie some of the phenotypic changes associated with this polymorphism.

Indexed as

Amino Acid SubstitutionMutation, MissenseAnimalsGenome-Wide Association StudyHumansMultiprotein ComplexesOocytesPolymorphism, GeneticProtein SubunitsReceptors, NicotinicSignal TransductionXenopus laevisMultiprotein ComplexesProtein SubunitsReceptors, Nicotinic

Identifiers

PMID22665477
PMCPMC3408138
OpenAlexW2077761422

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.