Evidence map›Paper›PMID 27009233›Full record

ArticleMolecular pharmacology2016

Mechanisms of Biased β-Arrestin-Mediated Signaling Downstream from the Cannabinoid 1 Receptor.

Francheska Delgado-Peraza, Kwang H Ahn, Carlos Nogueras-Ortiz, Imran N Mungrue, Ken Mackie, Debra A Kendall, Guillermo A Yudowski

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Pharmacological Evaluation of Cannabinoid Receptor Modulators Using GRABInternational journal of molecular sciences · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Cannabinoid Tolerance in S426A/S430A xThe Journal of pharmacology and experimental therapeutics · 2023
    Article
  11. Cannabinoid 1 (CBBritish journal of pharmacology · 2023
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. CB1 Cannabinoid Receptor Signaling and Biased Signaling.Molecules (Basel, Switzerland) · 2021
    Review
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Francheska Delgado-PerazaDepartment of Anatomy and Neurobiology (F.D.-P., G.A.Y.) and Institute of Neurobiology (F.D.-P., C.N.-O., G.A.Y.), University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (K.H.A., D.A.K.); Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (I.N.M.); and Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana (K.M.).
Kwang H AhnDepartment of Anatomy and Neurobiology (F.D.-P., G.A.Y.) and Institute of Neurobiology (F.D.-P., C.N.-O., G.A.Y.), University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (K.H.A., D.A.K.); Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (I.N.M.); and Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana (K.M.).
Carlos Nogueras-OrtizDepartment of Anatomy and Neurobiology (F.D.-P., G.A.Y.) and Institute of Neurobiology (F.D.-P., C.N.-O., G.A.Y.), University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (K.H.A., D.A.K.); Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (I.N.M.); and Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana (K.M.).
Imran N MungrueDepartment of Anatomy and Neurobiology (F.D.-P., G.A.Y.) and Institute of Neurobiology (F.D.-P., C.N.-O., G.A.Y.), University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (K.H.A., D.A.K.); Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (I.N.M.); and Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana (K.M.).
Ken MackieDepartment of Anatomy and Neurobiology (F.D.-P., G.A.Y.) and Institute of Neurobiology (F.D.-P., C.N.-O., G.A.Y.), University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (K.H.A., D.A.K.); Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (I.N.M.); and Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana (K.M.).
Debra A KendallDepartment of Anatomy and Neurobiology (F.D.-P., G.A.Y.) and Institute of Neurobiology (F.D.-P., C.N.-O., G.A.Y.), University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (K.H.A., D.A.K.); Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (I.N.M.); and Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana (K.M.).
Guillermo A YudowskiDepartment of Anatomy and Neurobiology (F.D.-P., G.A.Y.) and Institute of Neurobiology (F.D.-P., C.N.-O., G.A.Y.), University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (K.H.A., D.A.K.); Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (I.N.M.); and Department of Psychological & Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, Indiana (K.M.) Guillermo.yudowski@upr.edu debra.kendall@uconn.edu.
University of Puerto Rico, Medical Sciences Campus · PRIndiana University Bloomington · USUniversity of Connecticut · US

Funding

The Role of Sensory Input to Mammalian Locomotion After the Loss of supraspinal.P20GM103642 · NIGMS · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI LASALDE-DOMINICCI, JOSE ANTONIO · 2013 to 2023
$20.6M
TRANSLATIONAL PROTEOMICS CENTERG12MD007600 · NIMHD · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI FERNANDEZ-REPOLLET, EMMA · 2012 to 2016
$11.0M
Vascular and Cardiac Function Core - "Mentoring in Cardiovascular BiologyP30GM106392 · NIGMS · LSU HEALTH SCIENCES CENTER · PI KAPUSTA, DANIEL R · 2014 to 2018
$5.5M
Neuronal cannabinoidsR01DA011322 · NIDA · UNIVERSITY OF WASHINGTON · PI MACKIE, KENNETH · 1998 to 2014
$3.4M
Endocytic mechanisms controlling functional selectivity of the CB1RR01DA037924 · NIDA · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI SOSA, MARIA A · 2014 to 2018
$1.7M
Determinants of the Cannabinoid Receptor Life CycleR01DA020763 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI KENDALL, DEBRA A · 2007 to 2011
$1.5M
Cannabinoid Modulation of Cell FunctionK05DA021696 · NIDA · TRUSTEES OF INDIANA UNIVERSITY · PI MACKIE, KENNETH · 2007 to 2017
$1.3M
Regulation of GPCR Recycling at the Plasma MembraneR00DA023444 · NIDA · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI YUDOWSKI, GUILLERMO ARIEL · 2011 to 2013
$723k
Determining roles of the pro-apoptotic UPR gene CHAC1 in atherosclerosis.R00HL094709 · NHLBI · LSU HEALTH SCIENCES CENTER · PI MUNGRUE, IMRAN · 2012 to 2014
$722k
Determining roles of the pro-apoptotic UPR gene CHAC1 in atherosclerosis.K99HL094709 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MUNGRUE, IMRAN · 2009 to 2010
$179k
Regulation of GPCR Recycling at the Plasma MembraneK99DA023444 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YUDOWSKI, GUILLERMO ARIEL · 2007 to 2008
$173k
NHLBI NIH HHS K99 HL094709NHLBI NIH HHS R00 HL094709NIDA NIH HHS K05 DA021696NIDA NIH HHS K99 DA023444NIDA NIH HHS R00 DA023444NIDA NIH HHS R01 DA011322NIDA NIH HHS R01 DA020763NIDA NIH HHS R01 DA037924NIGMS NIH HHS P20 GM103642NIGMS NIH HHS P30 GM106392NIMHD NIH HHS G12 MD007600
6 · The paper itself

Abstract

Activation of G protein-coupled receptors results in multiple waves of signaling that are mediated by heterotrimeric G proteins and the scaffolding proteins β-arrestin 1/2. Ligands can elicit full or subsets of cellular responses, a concept defined as ligand bias or functional selectivity. However, our current understanding of β-arrestin-mediated signaling is still very limited. Here we provide a comprehensive view of β-arrestin-mediated signaling from the cannabinoid 1 receptor (CB1R). By using a signaling biased receptor, we define the cascades, specific receptor kinases, and molecular mechanism underlying β-arrestin-mediated signaling: We identify the interaction kinetics of CB1R and β-arrestin 1 during their endocytic trafficking as directly proportional to its efficacy. Finally, we demonstrate that signaling results in the control of genes clustered around prosurvival and proapoptotic functions among others. Together, these studies constitute a comprehensive description of β-arrestin-mediated signaling from CB1Rs and suggest modulation of receptor endocytic trafficking as a therapeutic approach to control β-arrestin-mediated signaling.

Indexed as

Signal TransductionArachidonic AcidsBenzoxazinesbeta-ArrestinsEndocannabinoidsGlyceridesG-Protein-Coupled Receptor KinasesHEK293 CellsHumansMorpholinesMutant ProteinsNaphthalenesProtein BindingProtein IsoformsProtein KinasesReceptor, Cannabinoid, CB1(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanoneArachidonic AcidsBenzoxazinesbeta-ArrestinsEndocannabinoidsGlyceridesglyceryl 2-arachidonateG-protein-coupled receptor kinase 6G-Protein-Coupled Receptor KinasesMorpholinesMutant ProteinsNaphthalenesProtein IsoformsProtein KinasesReceptor, Cannabinoid, CB1RNA, Messenger

Identifiers

PMID27009233
PMCPMC4885504
OpenAlexW2306894756

What OpenQuestion holds

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LicenceCC BY-NC
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.