ArticlePloS one2012
Receptor heteromerization expands the repertoire of cannabinoid signaling in rodent neurons.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026Review
- Emerging roles of cannabinoid pathways in renal injury and repair.Frontiers in pharmacology · 2026Review
- Kratom Alkaloids, Cannabinoids, and Chronic Pain: Basis of Potential Utility and Role in Therapy.Cannabis and cannabinoid research · 2025Article
- Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity.Cell reports · 2025Article
- Regulation of Cannabinoid and Opioid Receptor Levels by Endogenous and Pharmacological Chaperones.The Journal of pharmacology and experimental therapeutics · 2024Article
- Pharmacological Characterization of the Endocannabinoid Sensor GRABCannabis and cannabinoid research · 2024Article
- Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity.bioRxiv : the preprint server for biology · 2024Article
- Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches.Brain sciences · 2024Review
- Epidemiological overview of multidimensional chromosomal and genome toxicity of cannabis exposure in congenital anomalies and cancer development.Scientific reports · 2021Article
- Review of the Endocannabinoid System.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2021Review
- In vivo mapping of a GPCR interactome using knockin mice.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Activation of µ-δ opioid receptor heteromers inhibits neuropathic pain behavior in rodents.Pain · 2020Article
- Cannabinoids Exacerbate Alcohol Teratogenesis by a CB1-Hedgehog Interaction.Scientific reports · 2019Article
- Targeting Cannabinoid 1 and Delta Opioid Receptor Heteromers Alleviates Chemotherapy-Induced Neuropathic Pain.ACS pharmacology & translational science · 2019Article
- Cannabinoid Signaling in the Skin: Therapeutic Potential of the "C(ut)annabinoid" System.Molecules (Basel, Switzerland) · 2019Review
- Receptor-Receptor Interactions as a Widespread Phenomenon: Novel Targets for Drug Development?Frontiers in endocrinology · 2019Review
- Allosterism withinMolecular pharmacology · 2018Article
- Signaling within Allosteric Machines: Signal Transmission Pathways Inside G Protein-Coupled Receptors.Molecules (Basel, Switzerland) · 2017Review
- Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics.ACS chemical neuroscience · 2017Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
A fundamental question in G protein coupled receptor biology is how a single ligand acting at a specific receptor is able to induce a range of signaling that results in a variety of physiological responses. We focused on Type 1 cannabinoid receptor (CB₁R) as a model GPCR involved in a variety of processes spanning from analgesia and euphoria to neuronal development, survival and differentiation. We examined receptor dimerization as a possible mechanism underlying expanded signaling responses by a single ligand and focused on interactions between CB₁R and delta opioid receptor (DOR). Using co-immunoprecipitation assays as well as analysis of changes in receptor subcellular localization upon co-expression, we show that CB₁R and DOR form receptor heteromers. We find that heteromerization affects receptor signaling since the potency of the CB₁R ligand to stimulate G-protein activity is increased in the absence of DOR, suggesting that the decrease in CB₁R activity in the presence of DOR could, at least in part, be due to heteromerization. We also find that the decrease in activity is associated with enhanced PLC-dependent recruitment of arrestin3 to the CB₁R-DOR complex, suggesting that interaction with DOR enhances arrestin-mediated CB₁R desensitization. Additionally, presence of DOR facilitates signaling via a new CB₁R-mediated anti-apoptotic pathway leading to enhanced neuronal survival. Taken together, these results support a role for CB₁R-DOR heteromerization in diversification of endocannabinoid signaling and highlight the importance of heteromer-directed signal trafficking in enhancing the repertoire of GPCR signaling.
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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.