Evidence map›Paper›PMID 28319053›Full record

ArticleThe Journal of clinical investigation2017

Alternatively spliced mu opioid receptor C termini impact the diverse actions of morphine.

Jin Xu, Zhigang Lu, Ankita Narayan, Valerie P Le Rouzic, Mingming Xu, Amanda Hunkele, Taylor G Brown, William F Hoefer, Grace C Rossi, Richard C Rice and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Photo-affinity and Metabolic Labeling Probes Based on the Opioid Alkaloids.Chembiochem : a European journal of chemical biology · 2024
    Article
  7. Extracellular vesicle-mediated delivery of anti-miR-106b inhibits morphine-induced primary ciliogenesis in the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  8. Article
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  10. Article
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  15. 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

16 authors at 6 institutions in 2 countries.

Jin Xu
Zhigang Lu
Ankita Narayan
Valerie P Le Rouzic
Mingming Xu
Amanda Hunkele
Taylor G Brown
William F Hoefer
Grace C Rossi
Richard C Rice
Arlene Martínez-Rivera
Anjali M Rajadhyaksha
Luca Cartegni
Daniel L Bassoni
Gavril W Pasternak
Ying-Xian Pan
Memorial Sloan Kettering Cancer Center · USCornell University · USLong Island University · USDiscoveRx (United States) · USNanjing University of Chinese Medicine · CNRutgers, The State University of New Jersey · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
TRAINING IN BEHAV. PHARMACOLOGY OF HUMAN DRUG DEPENDENCET32DA007242 · NIDA · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI HEIL, SARAH H, HIGGINS, STEPHEN T · 1990 to 2025
$8.2M
Synthesis &Pharmacology of Novel Opiates and SystemsR01DA006241 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1990 to 2018
$6.4M
PHARMACOLOGY OF OPIOID RECEPTOR SUBTYPESR01DA007242 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1991 to 2022
$6.0M
Characterizing exon 11 promoter of the mu opioid receptor gene, OPRMR01DA013997 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 2002 to 2012
$3.3M
The Role of Cav1.2 L-type Ca2+ Channels in Cocaine-Induced ReinstatementR01DA029122 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI RAJADHYAKSHA, ANJALI M · 2012 to 2016
$2.1M
PHARMACOLOGY OF OPIOID RECEPTOR SUBTYPESR37DA007242 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PASTERNAK, GAVRIL W · 1996 to 2004
$1.5M
Exploring functions of mu opioid receptor carboxyl termini by gene targetingR21DA029244 · NIDA · SLOAN-KETTERING INST CAN RESEARCH · PI PAN, YING-XIAN · 2010 to 2011
$522k
Exploring function of mu opioid receptor splice variants in rat by gene targetingR21DA040858 · NIDA · SLOAN-KETTERING INST CAN RESEARCH · PI PAN, YING-XIAN · 2016 to 2017
$471k
NCI NIH HHS P30 CA008748NIDA NIH HHS R01 DA006241NIDA NIH HHS R01 DA007242NIDA NIH HHS R01 DA013997NIDA NIH HHS R01 DA029122NIDA NIH HHS R21 DA029244NIDA NIH HHS R21 DA040858NIDA NIH HHS R37 DA007242NIDA NIH HHS T32 DA007242
6 · The paper itself

Abstract

Extensive 3' alternative splicing of the mu opioid receptor gene OPRM1 creates multiple C-terminal splice variants. However, their behavioral relevance remains unknown. The present study generated 3 mutant mouse models with truncated C termini in 2 different mouse strains, C57BL/6J (B6) and 129/SvEv (129). One mouse truncated all C termini downstream of Oprm1 exon 3 (mE3M mice), while the other two selectively truncated C-terminal tails encoded by either exon 4 (mE4M mice) or exon 7 (mE7M mice). Studies of these mice revealed divergent roles for the C termini in morphine-induced behaviors, highlighting the importance of C-terminal variants in complex morphine actions. In mE7M-B6 mice, the exon 7-associated truncation diminished morphine tolerance and reward without altering physical dependence, whereas the exon 4-associated truncation in mE4M-B6 mice facilitated morphine tolerance and reduced morphine dependence without affecting morphine reward. mE7M-B6 mutant mice lost morphine-induced receptor desensitization in the brain stem and hypothalamus, consistent with exon 7 involvement in morphine tolerance. In cell-based studies, exon 7-associated variants shifted the bias of several mu opioids toward β-arrestin 2 over G protein activation compared with the exon 4-associated variant, suggesting an interaction of exon 7-associated C-terminal tails with β-arrestin 2 in morphine-induced desensitization and tolerance. Together, the differential effects of C-terminal truncation illustrate the pharmacological importance of OPRM1 3' alternative splicing.

Indexed as

Alternative SplicingAnalgesics, OpioidAnimalsBrainCodon, NonsenseDose-Response Relationship, DrugDrug ToleranceExonsGastrointestinal TransitGuanosine 5'-O-(3-Thiotriphosphate)LocomotionMaleMice, 129 StrainMice, Inbred C57BLMorphineMorphine DependenceAnalgesics, OpioidCodon, NonsenseGuanosine 5'-O-(3-Thiotriphosphate)MorphineOprm protein, mouseProtein IsoformsReceptors, Opioid, mu

Identifiers

PMID28319053
PMCPMC5373896
OpenAlexW2596715715

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.