ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Chronic morphine treatment inhibits opioid receptor desensitization and internalization.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 71 citations in OpenAlex.
- Addition of a second opioid may improve opioid response in cancer pain: preliminary data.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2004Trial
- Positive Emotion Regulation in Addiction: A New Frontier for Recovery Science.Current addiction reports · 2026Review
- Development of a novel cell-based, In-Cell Western/ERK assay system for the high-throughput screening of agonists acting on the delta-opioid receptor.Frontiers in pharmacology · 2022Article
- Exploration of beta-arrestin isoform signaling pathways in delta opioid receptor agonist-induced convulsions.Frontiers in pharmacology · 2022Article
- β-Arrestin-dependent ERK signaling reduces anxiety-like and conditioned fear-related behaviors in mice.Science signaling · 2021Article
- Spinal Opioid Tolerance Depends upon Platelet-Derived Growth Factor Receptor-Molecular pharmacology · 2020Article
- Opioids: Modulators of angiogenesis in wound healing and cancer.Oncotarget · 2017Review
- Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment.The international journal of neuropsychopharmacology · 2016Article
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Role for engagement of β-arrestin2 by the transactivated EGFR in agonist-specific regulation of δ receptor activation of ERK1/2.British journal of pharmacology · 2015Article
- β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia.Handbook of experimental pharmacology · 2014Review
- Opioid-induced mitogen-activated protein kinase signaling in rat enteric neurons following chronic morphine treatment.PloS one · 2014Article
- Ligand-induced μ opioid receptor internalization in enteric neurons following chronic treatment with the opiate fentanyl.Journal of neuroscience research · 2013Article
- Chronic morphine treatment attenuates cell growth of human BT474 breast cancer cells by rearrangement of the ErbB signalling network.PloS one · 2013Article
- Neuropsychological Functions of μ- and δ-Opioid Systems.ISRN Addiction · 2013Review
- Disruption of δ-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.Neuroscience bulletin · 2012Article
- Inhibition of Activity of GABA Transporter GAT1 by δ-Opioid Receptor.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- Pleiotropic opioid regulation of spinal endomorphin 2 release and its adaptations to opioid withdrawal are sexually dimorphic.The Journal of pharmacology and experimental therapeutics · 2012Article
- Article
- Regulation of opioid receptor signalling: implications for the development of analgesic tolerance.Molecular brain · 2011Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic opioid receptor (OR) activation by morphine causes distinct cellular adaptations responsible for the development of tolerance. The present study examines the effect of chronic morphine exposure on the ability of high-efficacy agonists to mediate delta-OR (DOR) and mu-OR (MOR) uncoupling and internalization, two regulatory mechanisms contributing to rapid desensitization of OR function. Chronic morphine treatment (1 microm; 72 hr) of DOR carrying neuroblastoma x glioma (NG108-15) hybrid cells, a prototypical model system frequently used to study cellular aspects of opioid tolerance, completely blocked the capacity of [d-Ala2, d-Leu5]enkephalin (DADLE) and etorphine to desensitize opioid-stimulated [35S]GTPgammaS binding and to mediate DOR internalization. Similar findings were obtained on stably DOR- and MOR-transfected human embryonic kidney (HEK) 293 cells. Chronic morphine treatment also heterologously impaired agonist regulation of non-opioid G-protein-coupled receptors, such as the m(4)-muscarinic acetylcholine receptor and the brain-type cannabinoid receptor. As a possible underlying mechanism, we found that chronic morphine treatment completely blocked agonist-induced redistribution of beta-arrestin1 in both NG108-15 and stably MOR-transfected HEK293 cells. Moreover, attenuation of beta-arrestin1 function appears to depend on persistent stimulation of MAP kinase activity during the course of chronic morphine treatment, because coincubation of the cells together with the MAP kinase blocker PD98059 fully restored beta-arrestin1 translocation and receptor internalization. These results demonstrate that chronic morphine treatment produces adaptational changes at the beta-arrestin1 level, which in turn attenuates agonist-mediated desensitization and internalization of G-protein-coupled receptors.
Indexed as
Identifiers
12451120PMC6758738W1776637350What 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.