Evidence map›Paper›PMID 26096047›Full record

ArticleCNS neuroscience & therapeutics2015

Modulation of mTOR Activity by μ-Opioid Receptor is Dependent upon the Association of Receptor and FK506-Binding Protein 12.

Yan Wang, Yan-Hui Ge, Yan-Xia Wang, Ting Liu, Ping-Yee Law, Horace H Loh, Hong-Zhuan Chen, Yu Qiu

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

Article in CNS neuroscience & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 11 citations in OpenAlex.

  1. 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 2 institutions in 2 countries.

Yan WangDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yan-Hui GeDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yan-Xia WangDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ting LiuDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ping-Yee LawDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Horace H LohDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Hong-Zhuan ChenDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yu QiuDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Jiao Tong University · CNUniversity of Minnesota · US

Funding

Subcellular Targeting/Packaging of Opioids/ReceptorsP50DA011806 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI WICKMAN, KEVIN D · 1998 to 2012
$14.0M
G-PROTEINS AND OPIOID RECEPTOR FUNCTIONSR01DA007339 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI LAW, PING-YEE · 1991 to 2008
$2.5M
NIDA NIH HHS DA007339NIDA NIH HHS DA011806NIDA NIH HHS P50 DA011806NIDA NIH HHS R01 DA007339
6 · The paper itself

Abstract

aimsMechanistic/mammalian target of rapamycin (mTOR) activation by μ-opioid receptor (OPRM1) participates in antinociceptive tolerance, hyperalgesia, and physical dependence. Our previous study also showed that mTOR activation by OPRM1 could attenuate β amyloid oligomers-induced neurotoxicity. OPRM1 is demonstrated to interact with FK506-binding protein 12 (FKBP12). It is our great interest to investigate whether OPRM1-mediated mTOR signaling is related to receptor-FKBP12 association.

methodsThe activities of mTOR and its downstream effector p70 S6K were measured by immunoblotting their phosphorylation status. The interaction of receptor with mTOR was detected by co-immunoprecipitation and immunofluorescence.

resultsOPRM1 activation by morphine-induced time-dependent mTOR activation. PI3K-specific inhibitor LY294002 only blocked the late phase of mTOR activation. However, morphine-induced mTOR activation was totally blocked at all time points in cells expressing FKBP12 association-deficient mutant receptor. FKBP12 knockdown also blocked morphine-induced mTOR activation. Further analysis demonstrated that morphine treatment enhanced the association of receptor with phosphorylated mTOR, whereas decreased association was observed after FKBP12 knockdown, mTOR inhibition or in cells expressing FKBP12 association-deficient mutant.

conclusionsOPRM1-FKBP12 association played a key role in OPRM1-mediated mTOR activation, which could underlie the mechanisms of multiple physiological and pathological processes. Thus, our findings provide new avenue to modulating these processes.

Indexed as

Analgesics, OpioidHEK293 CellsHumansImmunoprecipitationMorphineReceptors, Opioid, muRNA, Small InterferingSignal TransductionTacrolimus Binding Protein 1ATOR Serine-Threonine KinasesTransfectionAnalgesics, OpioidMorphineMTOR protein, humanOPRM1 protein, humanReceptors, Opioid, muRNA, Small InterferingTacrolimus Binding Protein 1ATOR Serine-Threonine KinasesFK506-binding protein 12Mechanistic/mammalian target of rapamycinProtein interactionμ-opioid receptor

Identifiers

PMID26096047
PMCPMC4477277
OpenAlexW1589375853

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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.