ArticleBritish journal of pharmacology2004
G-protein receptor kinase 3 (GRK3) influences opioid analgesic tolerance but not opioid withdrawal.
Article in British journal of pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 97 citations in OpenAlex.
- Prenatal fentanyl exposure affects social dominance and myelination patterns in the adult mouse brain.Neuropharmacology · 2025Article
- Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos.Development (Cambridge, England) · 2024Article
- Genetic mouse models in opioid research: current status and future directions.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Mechanisms of cannabinoid tolerance.Biochemical pharmacology · 2023Review
- A collection of cannabinoid-related negative findings from autaptic hippocampal neurons.Scientific reports · 2023Article
- G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Influence of G protein-biased agonists of μ-opioid receptor on addiction-related behaviors.Pharmacological reports : PR · 2021Review
- Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?Cellular and molecular neurobiology · 2021Review
- Review
- Review
- Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells.Scientific reports · 2020Article
- Post-translational Modifications of Opioid Receptors.Trends in neurosciences · 2020Review
- A cellular perspective of bias at G protein-coupled receptors.Protein science : a publication of the Protein Society · 2020Review
- Toward Directing Opioid Receptor Signaling to Refine Opioid Therapeutics.Biological psychiatry · 2020Review
- Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment.Neuroscience and biobehavioral reviews · 2019Review
- Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects.Nature communications · 2019Article
- Estrogen Regulation of GRK2 Inactivates Kappa Opioid Receptor Signaling Mediating Analgesia, But Not Aversion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Spinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.Pharmacological research · 2017Article
- Effect of Tamoxifen and Brain-Penetrant Protein Kinase C and c-Jun N-Terminal Kinase Inhibitors on Tolerance to Opioid-Induced Respiratory Depression in Mice.The Journal of pharmacology and experimental therapeutics · 2017Article
- The dark side of opioids in pain management: basic science explains clinical observation.Pain reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
1. Tolerance to opioids frequently follows repeated drug administration and affects the clinical utility of these analgesics. Studies in simple cellular systems have demonstrated that prolonged activation of opioid receptors produces homologous receptor desensitization by G-protein receptor kinase mediated receptor phosphorylation and subsequent beta-arrestin binding. To define the role of this regulatory mechanism in the control of the electrophysiological and behavioral responses to opioids, we used mice having a targeted disruption of the G-protein receptor kinase 3 (GRK3) gene. 2. Mice lacking GRK3 did not differ from wild-type littermates neither in their response latencies to noxious stimuli on the hot-plate test nor in their acute antinociceptive responses to fentanyl or morphine. 3. Tolerance to the electrophysiological response to the opioid fentanyl, measured in vitro in the hippocampus, was blocked by GRK3 deletion. In addition, tolerance to the antinociceptive effects of fentanyl was significantly reduced in GRK3 knockouts compared to wild-type littermate controls. 4. Tolerance to the antinociceptive effects of morphine was not affected by GRK3 deletion although morphine tolerance in hippocampal slices from GRK3 knockout mice was significantly inhibited. Tolerance developed more slowly in vitro to morphine than fentanyl supporting previous work in in vitro systems showing a correlation between agonist efficacy and GRK3-mediated desensitization. 5. The results of these studies suggest that GRK3-mediated mechanisms are important components of both electrophysiologic and behavioral opioid tolerance. Fentanyl, a high efficacy opioid, more effectively produced GRK3-dependent effects than morphine, a low efficacy agonist.
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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.