ArticleThe Journal of biological chemistry2011
Heteromultimerization of cannabinoid CB(1) receptor and orexin OX(1) receptor generates a unique complex in which both protomers are regulated by orexin A.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 92 citations in OpenAlex.
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- Coactivation of CB1 and GPR55 promotes GABA release and motor behavior at striatonigral terminals through increased dimerization induced by CB1 activation.Frontiers in molecular neuroscience · 2026Article
- Dual Role of the Spinal Endocannabinoid System in Response to Noxious Stimuli: Antinociceptive Pathways and Neuropathic Pain Mechanisms.International journal of molecular sciences · 2025Review
- In Vitro Signaling Properties of Cannabinoid and Orexin Receptors: How Orexin Receptors Influence Cannabinoid Receptor-Mediated Signaling.Pharmacology research & perspectives · 2025Article
- Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024Review
- Cannabinoid and Orexigenic Systems Interplay as a New Focus of Research in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Dual Cannabinoid and Orexin Regulation of Anhedonic Behaviour Caused by Prolonged Restraint Stress.Brain sciences · 2023Article
- Endocannabinoid-Binding Receptors as Drug Targets.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo.Translational psychiatry · 2022Article
- Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles.Biomedicines · 2022Review
- Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition.Cells · 2022Review
- The role of basolateral amygdala orexin 1 receptors on the modulation of pain and psychosocial deficits in nitroglycerin-induced migraine model in adult male rats.The Korean journal of pain · 2022Article
- Orexin Signaling: A Complex, Multifaceted Process.Frontiers in cellular neuroscience · 2022Review
- Article
- New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling.Frontiers in pharmacology · 2020Review
- Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective.Frontiers in neurology · 2020Review
- Cannabinoid Signaling in the Skin: Therapeutic Potential of the "C(ut)annabinoid" System.Molecules (Basel, Switzerland) · 2019Review
- Therapeutic targeting of HER2-CBProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Design, Synthesis, and Evaluation of a Diazirine Photoaffinity Probe for Ligand-Based Receptor Capture Targeting G Protein-Coupled Receptors.Molecular pharmacology · 2019Article
- Orexin A/Hypocretin Modulates Leptin Receptor-Mediated Signaling by Allosteric Modulations Mediated by the Ghrelin GHS-R1A Receptor in Hypothalamic Neurons.Molecular neurobiology · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Agonist-induced internalization was observed for both inducible and constitutively expressed forms of the cannabinoid CB(1) receptor. These were also internalized by the peptide orexin A, which has no direct affinity for the cannabinoid CB(1) receptor, but only when the orexin OX(1) receptor was co-expressed along with the cannabinoid CB(1) receptor. This effect of orexin A was concentration-dependent and blocked by OX(1) receptor antagonists. Moreover, the ability of orexin A to internalize the CB(1) receptor was also blocked by CB(1) receptor antagonists. Remarkably, orexin A was substantially more potent in producing internalization of the CB(1) receptor than in causing internalization of the bulk OX(1) receptor population, and this was true in cells in which the CB(1) receptor was maintained at a constant level, whereas levels of OX(1) could be varied and vice versa. Both co-immunoprecipitation and cell surface, homogenous time-resolved fluorescence resonance energy transfer based on covalent labeling of N-terminal "SNAP" and "CLIP" tags present in the extracellular N-terminal domain of the receptors confirmed the capacity of these two receptors to heteromultimerize. These studies confirm the capacity of the CB(1) and OX(1) receptors to interact directly and demonstrate that this complex has unique regulatory characteristics. The higher potency of the agonist orexin A to regulate the CB(1)-OX(1) heteromer compared with the OX(1)-OX(1) homomer present in the same cells and the effects of CB(1) receptor antagonists on the function of orexin A suggest an interplay between these two systems that may modulate appetite, feeding, and wakefulness.
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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.