ArticleMolecular neurobiology2016
Signaling Mechanism of Cannabinoid Receptor-2 Activation-Induced β-Endorphin Release.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Crosstalk between neurotransmitters and NLRP3 inflammasome pathway: A narrative review.Molecular biology reports · 2026Review
- Cannabinoid CBBritish journal of pharmacology · 2025Review
- Opioidergic Signaling-A Neglected, Yet Potentially Important Player in Atopic Dermatitis.International journal of molecular sciences · 2022Review
- Emerging roles of keratinocytes in nociceptive transduction and regulation.Frontiers in molecular neuroscience · 2022Review
- Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia.International journal of molecular sciences · 2021Review
- Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation.International journal of molecular sciences · 2021Review
- β-endorphin at the intersection of pain and cancer progression: Preclinical evidence.Neuroscience letters · 2021Article
- Peripheral Mechanisms of Neuropathic Pain-the Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Cannabinoid Signaling in the Skin: Therapeutic Potential of the "C(ut)annabinoid" System.Molecules (Basel, Switzerland) · 2019Review
- Cannabinoid CB2 Agonist AM1710 Differentially Suppresses Distinct Pathological Pain States and Attenuates Morphine Tolerance and Withdrawal.Molecular pharmacology · 2019Article
- Repurposing established cyclic adenosine monophosphate reducing agents for the prevention and therapy of epidermal growth factor receptor inhibitor resistance in non-small cell lung cancer.Translational lung cancer research · 2018Article
- Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics.Journal of pain research · 2017Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of cannabinoid receptor-2 (CB2) results in β-endorphin release from keratinocytes, which then acts on primary afferent neurons to inhibit nociception. However, the underlying mechanism is still unknown. The CB2 receptor is generally thought to couple to Gi/o to inhibit cAMP production, which cannot explain the peripheral stimulatory effects of CB2 receptor activation. In this study, we found that in a keratinocyte cell line, the Gβγ subunits from Gi/o, but not Gαs, were involved in CB2 receptor activation-induced β-endorphin release. Inhibition of MAPK kinase, but not PLC, abolished CB2 receptor activation-induced β-endorphin release. Also, CB2 receptor activation significantly increased intracellular Ca(2+). Treatment with BAPTA-AM or thapsigargin blocked CB2 receptor activation-induced β-endorphin release. Using a rat model of inflammatory pain, we showed that the MAPK kinase inhibitor PD98059 abolished the peripheral effect of the CB2 receptor agonist on nociception. We thus present a novel mechanism of CB2 receptor activation-induced β-endorphin release through Gi/o-Gβγ-MAPK-Ca(2+) signaling pathway. Our data also suggest that stimulation of MAPK contributes to the peripheral analgesic effect of CB2 receptor agonists.
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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.