ArticlePloS one2013
The second intracellular loop of the human cannabinoid CB2 receptor governs G protein coupling in coordination with the carboxyl terminal domain.
Article in PloS one, 2013. 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 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 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
- The Therapeutic Paradox of Endocannabinoid Immunomodulation: Molecular Mechanisms and Strategic Frameworks.International journal of molecular sciences · 2026Review
- Type-1 Cannabinoid Receptor Promiscuous Coupling: Computational Insights into Receptor-G Protein Interaction Dynamics.International journal of molecular sciences · 2025Article
- Exploring Endocannabinoid System: Unveiling New Roles in Modulating ER Stress.Antioxidants (Basel, Switzerland) · 2024Review
- CB2 stimulation of adipose resident ILC2s orchestrates immune balance and ameliorates type 2 diabetes mellitus.Cell reports · 2024Article
- Circadian clock organization in the retina: From clock components to rod and cone pathways and visual function.Progress in retinal and eye research · 2023Review
- Structural insights into the human niacin receptor HCA2-GNature communications · 2023Article
- Rational drug design of CB2 receptor ligands: from 2012 to 2021.RSC advances · 2022Review
- Recent Advances in Endocannabinoid System Targeting for Improved Specificity: Strategic Approaches to Targeted Drug Delivery.International journal of molecular sciences · 2022Review
- Characterization of hypotensive and vasorelaxant effects of PHAR-DBH-Me a new cannabinoid receptor agonist.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- Interactions of cone cannabinoid CB1 and dopamine D4 receptors increase day/night difference in rod-cone gap junction coupling in goldfish retina.The Journal of physiology · 2021Article
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- Structure-Effect Relationships of Novel Semi-Synthetic Cannabinoid Derivatives.Frontiers in pharmacology · 2019Article
- New Insights in Cannabinoid Receptor Structure and Signaling.Current molecular pharmacology · 2019Review
- Structural basis for GPR40 allosteric agonism and incretin stimulation.Nature communications · 2018Article
- Endocannabinod Signal Dysregulation in Autism Spectrum Disorders: A Correlation Link between Inflammatory State and Neuro-Immune Alterations.International journal of molecular sciences · 2017Review
- Chronic activation of CB2 cannabinoid receptors in the hippocampus increases excitatory synaptic transmission.The Journal of physiology · 2015Article
- Cellular signalling of non-synonymous single-nucleotide polymorphisms of the human μ-opioid receptor (OPRM1).British journal of pharmacology · 2015Review
- Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 receptor-Gi protein complex.The Journal of biological chemistry · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The major effects of cannabinoids and endocannabinoids are mediated via two G protein-coupled receptors, CB1 and CB2, elucidation of the mechanism and structural determinants of the CB2 receptor coupling with G proteins will have a significant impact on drug discovery. In the present study, we systematically investigated the role of the intracellular loops in the interaction of the CB2 receptor with G proteins using chimeric receptors alongside the characterization of cAMP accumulation and ERK1/2 phosphorylation. We provided evidence that ICL2 was significantly involved in G protein coupling in coordination with the C-terminal end. Moreover, a single alanine substitution of the Pro-139 in the CB2 receptor that corresponds to Leu-222 in the CB1 receptor resulted in a moderate impairment in the inhibition of cAMP accumulation, whereas mutants P139F, P139M and P139L were able to couple to the Gs protein in a CRE-driven luciferase assay. With the ERK activation experiments, we further found that P139L has the ability to activate ERK through both Gi- and Gs-mediated pathways. Our findings defined an essential role of the second intracellular loop of the CB2 receptor in coordination with the C-terminal tail in G protein coupling and receptor activation.
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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.