Evidence map›Paper›PMID 26947945›Full record

ArticleNeuropharmacology2016

Selective chemical genetic inhibition of protein kinase C epsilon reduces ethanol consumption in mice.

Rajani Maiya, Thomas McMahon, Dan Wang, Benjamin Kanter, Dev Gandhi, Holly L Chapman, Jacklyn Miller, Robert O Messing

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

Article in Neuropharmacology, 2016. 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
0.3field-weighted citation impact, top 32% 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, 10 citations in OpenAlex.

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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 2 institutions in 1 country.

Rajani MaiyaDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 78712, USA.
Thomas McMahonThe Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.
Dan WangThe Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.
Benjamin KanterThe Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.
Dev GandhiDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 78712, USA.
Holly L ChapmanDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 78712, USA.
Jacklyn MillerThe Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.
Robert O MessingDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 78712, USA; The Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA. Electronic address: romessing@austin.utexas.edu.
University of California, San Francisco · USThe University of Texas at Austin · US

Funding

Vector, Transgenic, and Imaging CoreP50AA017072 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RON, DORIT · 2008 to 2017
$13.9M
Regulation of GABAA Receptors by PKC epsilon.R37AA013588 · NIAAA · ERNEST GALLO CLINIC AND RESEARCH CENTER · PI MESSING, ROBERT O. · 2003 to 2011
$3.7M
Regulation of GABAA Receptors by PKC epsilon.R01AA013588 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI MESSING, ROBERT O. · 2002 to 2016
$1.9M
NIAAA NIH HHS P50 AA017072NIAAA NIH HHS R01 AA013588NIAAA NIH HHS R37 AA013588
6 · The paper itself

Abstract

Reducing expression or inhibiting translocation of protein kinase C epsilon (PKCε) prolongs ethanol intoxication and decreases ethanol consumption in mice. However, we do not know if this phenotype is due to reduced PKCε kinase activity or to impairment of kinase-independent functions. In this study, we used a chemical-genetic strategy to determine whether a potent and highly selective inhibitor of PKCε catalytic activity reduces ethanol consumption. We generated ATP analog-specific PKCε (AS-PKCε) knock-in mice harboring a point mutation in the ATP binding site of PKCε that renders the mutant kinase highly sensitive to inhibition by 1-tert-butyl-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine (1-NA-PP1). Systemically administered 1-NA-PP1 readily crossed the blood brain barrier and inhibited PKCε-mediated phosphorylation. 1-NA-PP1 reversibly reduced ethanol consumption by AS-PKCε mice but not by wild type mice lacking the AS-PKCε mutation. These results support the development of inhibitors of PKCε catalytic activity as a strategy to reduce ethanol consumption, and they demonstrate that the AS- PKCε mouse is a useful tool to study the role of PKCε in behavior.

Indexed as

Alcohol DrinkingAlcohol-Related DisordersAnimalsBlotting, WesternCentral Nervous System DepressantsEthanolGene Knock-In TechniquesInjections, IntraperitonealMaleMice, Inbred C57BLMice, TransgenicPhosphorylationPoint MutationProtein Kinase C-epsilonProtein Kinase InhibitorsPyrazoles1-tert-butyl-3-naphthalen-1-ylpyrazolo(3,4-d)pyrimidin-4-amineCentral Nervous System DepressantsEthanolGabrg2 protein, mousePrkce protein, mouseProtein Kinase C-epsilonProtein Kinase InhibitorsPyrazolesPyrimidinesReceptors, GABA-A1-NA-PP11-tert-butyl-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine (PubChem CID: 4877)AlcoholAS-KinaseEthanolProtein kinase C

Identifiers

PMID26947945
PMCPMC4912951
OpenAlexW2300452294

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.