ArticleCurrent biology : CB2008
Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence.
Article in Current biology : CB, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- A Balancing Act: Learning from the Past to Build a Future-Focused Opioid Strategy.Annual review of physiology · 2024Review
- Deletion of arrestin-3 does not reduce drug-seeking behavior in a longitudinal paradigm of oral morphine self-administration.Frontiers in pharmacology · 2024Article
- Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis.Journal of pharmaceutical analysis · 2023Article
- Mechanisms of cannabinoid tolerance.Biochemical pharmacology · 2023Review
- The Downregulation of Opioid Receptors and Neuropathic Pain.International journal of molecular sciences · 2023Review
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges.Frontiers in pharmacology · 2023Review
- Pharmacological and genetic manipulations at the µ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?Cellular and molecular neurobiology · 2021Review
- Convallatoxin enhance the ligand-induced mu-opioid receptor endocytosis and attenuate morphine antinociceptive tolerance in mice.Scientific reports · 2019Article
- History of Alcohol and Opioid Use Impacts on the Long-Term Recovery Trajectories of Methamphetamine-Dependent Patients.Frontiers in psychiatry · 2019Article
- Modulation of miR-139-5p on chronic morphine-induced, naloxone-precipitated cAMP overshoot in vitro.Metabolic brain disease · 2018Article
- Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain.Neural regeneration research · 2018Article
- Identification of the First Marine-Derived Opioid Receptor "Balanced" Agonist with a Signaling Profile That Resembles the Endorphins.ACS chemical neuroscience · 2017Article
- Change in functional selectivity of morphine with the development of antinociceptive tolerance.British journal of pharmacology · 2015Article
- Prolonged morphine treatment alters δ opioid receptor post-internalization trafficking.British journal of pharmacology · 2015Article
- Molecular Perspectives for mu/delta Opioid Receptor Heteromers as Distinct, Functional Receptors.Cells · 2014Article
- Functionally selective signaling for morphine and fentanyl antinociception and tolerance mediated by the rat periaqueductal gray.PloS one · 2014Article
- Opioid receptor desensitization: mechanisms and its link to tolerance.Frontiers in pharmacology · 2014Review
- An immunocytochemical-derived correlate for evaluating the bridging of heteromeric mu-delta opioid protomers by bivalent ligands.ACS chemical biology · 2013Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Opioid drugs, such as morphine, are among the most effective analgesics available. However, their utility for the treatment of chronic pain is limited by side effects including tolerance and dependence. Morphine acts primarily through the mu-opioid receptor (MOP-R) , which is also a target of endogenous opioids. However, unlike endogenous ligands, morphine fails to promote substantial receptor endocytosis both in vitro, and in vivo. Receptor endocytosis serves at least two important functions in signal transduction. First, desensitization and endocytosis act as an "off" switch by uncoupling receptors from G protein. Second, endocytosis functions as an "on" switch, resensitizing receptors by recycling them to the plasma membrane. Thus, both the off and on function of the MOP-R are altered in response to morphine compared to endogenous ligands. To examine whether the low degree of endocytosis induced by morphine contributes to tolerance and dependence, we generated a knockin mouse that expresses a mutant MOP-R that undergoes morphine-induced endocytosis. Morphine remains an excellent antinociceptive agent in these mice. Importantly, these mice display substantially reduced antinociceptive tolerance and physical dependence. These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence.
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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.