ArticleBritish journal of pharmacology2018
Tolerance to high-internalizing δ opioid receptor agonist is critically mediated by arrestin 2.
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- PN6047 Demonstrates Broad Preclinical Efficacy in Headache Models as a Novel Delta-Opioid Receptor Agonist.bioRxiv : the preprint server for biology · 2026Article
- An engineered trafficking biosensor reveals a role for DNAJC13 in DOR downregulation.Nature chemical biology · 2025Article
- Identification of 1,3,8-Triazaspiro[4.5]Decane-2,4-Dione Derivatives as a NovelThe Journal of pharmacology and experimental therapeutics · 2024Article
- The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway.Cells · 2024Article
- Review
- Receptor expression and signaling properties in the brain, and structural ligand motifs that contribute to delta opioid receptor agonist-induced seizures.Neuropharmacology · 2023Review
- Effects of chronic delta-opioid receptor agonist on the excitability of hippocampal glutamate and brainstem monoamine neurons, anxiety, locomotion, and habituation in rats.Pharmacological reports : PR · 2023Article
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- Opportunities and Challenges for In Silico Drug Discovery at Delta Opioid Receptors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Opioid-Induced Pronociceptive Signaling in the Gastrointestinal Tract Is Mediated by Delta-Opioid Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Exploration of beta-arrestin isoform signaling pathways in delta opioid receptor agonist-induced convulsions.Frontiers in pharmacology · 2022Article
- Identification of a Novel Delta Opioid Receptor Agonist Chemotype with Potential Negative Allosteric Modulator Capabilities.Molecules (Basel, Switzerland) · 2021Article
- Modulating β-arrestin 2 recruitment at the δ- and μ-opioid receptors using peptidomimetic ligands.RSC medicinal chemistry · 2021Article
- β-Arrestin-dependent ERK signaling reduces anxiety-like and conditioned fear-related behaviors in mice.Science signaling · 2021Article
- Article
- Natural Products for the Treatment of Pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide.Biochemistry · 2021Review
- A non-convulsant delta-opioid receptor agonist, KNT-127, reduces cortical spreading depression and nitroglycerin-induced allodynia.Headache · 2021Article
- Review
- Negative relationship between brain αExperimental brain research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeOpioid δ receptor agonists are potent antihyperalgesics in chronic pain models, but tolerance develops after prolonged use. Previous evidence indicates that distinct forms of tolerance occur depending on the internalization properties of δ receptor agonists. As arrestins are important in receptor internalization, we investigated the role of arrestin 2 (β-arrestin 1) in mediating the development of tolerance induced by high- and low-internalizing δ receptor agonists. EXPERIMENTAL APPROACH: We evaluated the effect of two δ receptor agonists with similar analgesic potencies, but either high-(SNC80) or low-(ARM390) internalization properties in wild-type (WT) and arrestin 2 knockout (KO) mice. We compared tolerance to the antihyperalgesic effects of these compounds in a model of inflammatory pain. We also examined tolerance to the convulsant effect of SNC80. Furthermore, effect of chronic treatment with SNC80 on δ agonist-stimulated [ KEY
resultsArrestin 2 KO resulted in increased drug potency, duration of action and decreased acute tolerance to the antihyperalgesic effects of SNC80. In contrast, ARM390 produced similar effects in both WT and KO animals. Following chronic treatment, we found a marked decrease in the extent of tolerance to SNC80-induced antihyperalgesia and convulsions in arrestin 2 KO mice. Accordingly, δ receptors remained functionally coupled to G proteins in arrestin 2 KO mice chronically treated with SNC80. CONCLUSIONS AND IMPLICATIONS: Overall, these results suggest that δ receptor agonists interact with arrestins in a ligand-specific manner, and tolerance to high- but not low-internalizing agonists are preferentially regulated by arrestin 2.
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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.