ArticleThe Journal of biological chemistry2013
Distinct roles of β-arrestin 1 and β-arrestin 2 in ORG27569-induced biased signaling and internalization of the cannabinoid receptor 1 (CB1).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- Phosphorylation site topology governs the functional dynamics of arrestin recruitment to GPCRs.Research square · 2026Article
- Beta arrestin 1 is a key regulator of pulmonary vascular tone.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multi-faceted roles of β-arrestins in G protein-coupled receptor endocytosis.Nature communications · 2025Article
- Molecular mechanism of the arrestin-biased agonism of neurotensin receptor 1 by an intracellular allosteric modulator.Cell research · 2025Article
- Article
- Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024Review
- Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.The Journal of pharmacology and experimental therapeutics · 2024Review
- Pharmacological Characterization of the Endocannabinoid Sensor GRABCannabis and cannabinoid research · 2024Article
- Myeloid beta-arrestin 2 depletion attenuates metabolic dysfunction-associated steatohepatitis via the metabolic reprogramming of macrophages.Cell metabolism · 2024Article
- The Development of Cannabinoids as Therapeutic Agents in the United States.Pharmacological reviews · 2024Review
- Comparing CB1 receptor GIRK channel responses to receptor internalization using a kinetic imaging assay.Scientific reports · 2024Article
- The NPXXY Motif Regulates β-Arrestin Recruitment by the CB1 Cannabinoid Receptor.Cannabis and cannabinoid research · 2023Article
- Cannabinoid Tolerance in S426A/S430A xThe Journal of pharmacology and experimental therapeutics · 2023Article
- Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Potential of dietary hemp and cannabinoids to modulate immune response to enhance health and performance in animals: opportunities and challenges.Frontiers in immunology · 2023Review
- Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions.Antioxidants (Basel, Switzerland) · 2022Review
- A critical review of cannabis in medicine and dentistry: A look back and the path forward.Clinical and experimental dental research · 2022Review
- Acute and long-term effects of cannabinoids on hypertension and kidney injury.Scientific reports · 2022Article
- CB1 Cannabinoid Receptor Signaling and Biased Signaling.Molecules (Basel, Switzerland) · 2021Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor primarily expressed in brain tissue that has been implicated in several disease states. CB1 allosteric compounds, such as ORG27569, offer enormous potential as drugs over orthosteric ligands, but their mechanistic, structural, and downstream effects upon receptor binding have not been established. Previously, we showed that ORG27569 enhances agonist binding affinity to CB1 but inhibits G protein-dependent agonist signaling efficacy in HEK293 cells and rat brain expressing the CB1 receptor (Ahn, K. H., Mahmoud, M. M., and Kendall, D. A. (2012) J. Biol. Chem. 287, 12070-12082). Here, we identify the mediators of CB1 receptor internalization and ORG27569-induced G protein-independent signaling. Using siRNA technology, we elucidate an ORG27569-induced signaling mechanism for CB1 wherein β-arrestin 1 mediates short term signaling to ERK1/2 with a peak at 5 min and other upstream kinase components including MEK1/2 and c-Src. Consistent with these findings, we demonstrate co-localization of CB1-GFP with red fluorescent protein-β-arrestin 1 upon ORG27569 treatment using confocal microscopy. In contrast, we show the critical role of β-arrestin 2 in CB1 receptor internalization upon treatment with CP55940 (agonist) or treatment with ORG27569. These results demonstrate for the first time the involvement of β-arrestin in CB1-biased signaling by a CB1 allosteric modulator and also define the differential role of the two β-arrestin isoforms in CB1 signaling and internalization.
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What OpenQuestion holds
Registered trials
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.