ArticleMolecular pharmacology2013
Differentiation of opioid drug effects by hierarchical multi-site phosphorylation.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 130 citations in OpenAlex.
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- EphB1 Receptor Blockade Augments Morphine Antinociception via Inhibiting GRK2-Mediated µ-Opioid Receptor Internalization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Role of the G protein-coupled receptor kinase 2/3 N terminus in discriminating the endocytic effects of opioid agonist drugs.Molecular pharmacology · 2025Article
- Key phosphorylation sites for robust β-arrestin2 binding at the MOR revisited.Communications biology · 2024Article
- Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures.Scientific reports · 2024Article
- Review
- Deletion of arrestin-3 does not reduce drug-seeking behavior in a longitudinal paradigm of oral morphine self-administration.Frontiers in pharmacology · 2024Article
- Review
- In situ visualization of opioid and cannabinoid drug effects using phosphosite-specific GPCR antibodies.Communications biology · 2023Article
- Delineation of G Protein-Coupled Receptor Kinase Phosphorylation Sites within the DInternational journal of molecular sciences · 2023Article
- Article
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- A bead-based GPCR phosphorylation immunoassay for high-throughput ligand profiling and GRK inhibitor screening.Communications biology · 2022Article
- How Arrestins and GRKs Regulate the Function of Long Chain Fatty Acid Receptors.International journal of molecular sciences · 2022Review
- Attenuated G protein signaling and minimal receptor phosphorylation as a biochemical signature of low side-effect opioid analgesics.Scientific reports · 2022Article
- CRISPR/Cas9 unveils the dynamics of the endogenous µ-opioid receptors on neuronal cells under continuous opioid stimulation.Pharmacology research & perspectives · 2022Article
- GPCR kinase knockout cells reveal the impact of individual GRKs on arrestin binding and GPCR regulation.Nature communications · 2022Article
- Magnesium and Morphine in the Treatment of Chronic Neuropathic Pain-A Biomedical Mechanism of Action.International journal of molecular sciences · 2021Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Differences in the ability of opioid drugs to promote regulated endocytosis of μ-opioid receptors are related to their tendency to produce drug tolerance and dependence. Here we show that drug-specific differences in receptor internalization are determined by a conserved, 10-residue sequence in the receptor's carboxyl-terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at serine (S)375, present in the middle of this sequence, but opioids differ markedly in their ability to drive higher-order phosphorylation on flanking residues [threonine (T)370, T376, and T379]. Multi-phosphorylation is required for the endocytosis-promoting activity of this sequence and occurs both sequentially and hierarchically, with S375 representing the initiating site. Higher-order phosphorylation involving T370, T376, and T379 specifically requires GRK2/3 isoforms, and the same sequence controls opioid receptor internalization in neurons. These results reveal a biochemical mechanism differentiating the endocytic activity of opioid drugs.
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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.