Evidence map›Paper›PMID 24607931›Full record

ArticleNeuroscience letters2014

Role of FK506 binding protein 12 in morphine-induced μ-opioid receptor internalization and desensitization.

Ying-Hui Yan, Yan Wang, Lan-Xue Zhao, Shan Jiang, Horace H Loh, Ping-Yee Law, Hong-Zhuan Chen, Yu Qiu

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

Article in Neuroscience letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. 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

8 authors at 2 institutions in 2 countries.

Ying-Hui Yan *Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Yan Wang *Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Lan-Xue ZhaoDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Shan JiangDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Horace H LohDepartment of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church St. S. E., Minneapolis, Minnesota, 55455, USA.
Ping-Yee LawDepartment of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church St. S. E., Minneapolis, Minnesota, 55455, USA.
Hong-Zhuan ChenDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Yu QiuDepartment of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, 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

Agonist-activated μ-opioid receptor (OPRM1) undergoes robust receptor phosphorylation by G protein-coupled receptor kinases and subsequent β-arrestin recruitment, triggering receptor internalization and desensitization. Morphine, a widely prescribed opioid, induces receptor phosphorylation inefficiently. Previously we reported that FK506 binding protein 12 (FKBP12) specifically interacts with OPRM1 and such interaction attenuates receptor phosphorylation and facilitates morphine-induced recruitment and activation of protein kinase C. In the current study, we demonstrated that the association of FKBP12 with OPRM1 also affects morphine-induced receptor internalization and G protein-dependent adenylyl cyclase desensitization. Morphine induced faster receptor internalization and adenylyl cyclase desensitization in cells expressing OPRM1 with Pro(353) mutated to Ala (OPRM1P353A), which does not interact with FKBP12, or in the presence of FK506 which dissociates the receptor-FKBP12 interaction. Furthermore, knockdown of cellular FKBP12 level by siRNA accelerated morphine-induced receptor internalization and adenylyl cyclase desensitization. Our study further demonstrated that peptidyl prolyl cis-trans isomerase activity of FKBP12 probably plays a role in inhibition of receptor phosphorylation. In the view that internalized receptor recycles and thus counteracts the development of analgesic tolerance, receptor's association with FKBP12 could also contribute to the development of morphine tolerance through modulation of receptor trafficking.

Indexed as

Adenylyl CyclasesHEK293 CellsHumansMorphineMutationPhosphorylationReceptors, Opioid, muRNA, Small InterferingTacrolimusTacrolimus Binding Protein 1AAdenylyl CyclasesMorphineOPRM1 protein, humanReceptors, Opioid, muRNA, Small InterferingTacrolimusTacrolimus Binding Protein 1ADesensitizationFK506 binding protein 12InternalizationMorphineμ-Opioid receptor

Identifiers

PMID24607931
PMCPMC4010564
OpenAlexW1964641891

What OpenQuestion holds

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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.