ArticleeLife2018
Cellular tolerance at the µ-opioid receptor is phosphorylation dependent.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
The trial behind it
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Neuropeptides as transmitters and regulators of the locus coeruleus noradrenergic system.Pharmacological reviews · 2025Review
- GPER Enhances Chronic Burn Pain via PKC-Mediated Mu-Opioid Receptor Phosphorylation in the Rostral Ventromedial Medulla.Journal of pain research · 2025Article
- Chronic morphine treatment induces sex- and synapse-specific cellular tolerance on thalamo-cortical mu opioid receptor signaling.Journal of neurophysiology · 2024Article
- Chronic Morphine Induces Adaptations in Opioid Receptor Signaling in a Thalamostriatal Circuit That Are Location Dependent, Sex Specific, and Regulated by μ-Opioid Receptor Phosphorylation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- Chronic morphine induces adaptations in opioid receptor signaling in a thalamo-cortico-striatal circuit that are projection-dependent, sex-specific and regulated by mu opioid receptor phosphorylation.bioRxiv : the preprint server for biology · 2023Article
- Article
- Agonist-Specific Regulation of G Protein-Coupled Receptors after Chronic Opioid Treatment.Molecular pharmacology · 2022Article
- Cellular Tolerance Induced by Chronic Opioids in the Central Nervous System.Frontiers in systems neuroscience · 2022Review
- Opioid Analgesia and Opioid-Induced Adverse Effects: A Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- G-Protein-Coupled Estrogen Receptor (GPER) in the Rostral Ventromedial Medulla Is Essential for Mobilizing Descending Inhibition of Itch.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Molecular mechanisms of opioid tolerance: From opioid receptors to inflammatory mediators (Review).Experimental and therapeutic medicine · 2021Review
- Relevance of Mu-Opioid Receptor Splice Variants and Plasticity of Their Signaling Sequelae to Opioid Analgesic Tolerance.Cellular and molecular neurobiology · 2021Review
- Aversive Stress Reduces Mu Opioid Receptor Expression in the Intercalated Nuclei of the Rat Amygdala.Cellular and molecular neurobiology · 2021Article
- Biased ligands at opioid receptors: Current status and future directions.Science signaling · 2021Review
- Review
- Opioid Pharmacology under the Microscope.Molecular pharmacology · 2020Review
- Recent Progress in Opioid Research from an Electrophysiological Perspective.Molecular pharmacology · 2020Review
- Chronic Treatment with Morphine Disrupts Acute Kinase-Dependent Desensitization of GPCRs.Molecular pharmacology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Phosphorylation of the μ-opioid receptor (MOR) is known as a key step in desensitization and internalization but the role in the development of long-term tolerance at the cellular level is not known. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in locus coeruleus neurons in a MOR knockout rat. Both receptors activated potassium conductance similar to endogenous receptors in wild type animals. The exWT receptors, like endogenous receptors, acutely desensitized, internalized and, after chronic morphine treatment, displayed signs of tolerance. However, TPD receptors did not desensitize or internalize with agonist treatment. In addition the TPD receptors did not develop cellular tolerance following chronic morphine treatment. Thus C-terminal phosphorylation is necessary for the expression of acute desensitization, trafficking and one sign of long-term tolerance to morphine at the cellular level.
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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.