ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Two distinct mechanisms mediate acute mu-opioid receptor desensitization in native neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. 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, 51 citations in OpenAlex.
- Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- Mechanistic diversity involved in the desensitization of G protein-coupled receptors.Archives of pharmacal research · 2021Review
- Recent Progress in Opioid Research from an Electrophysiological Perspective.Molecular pharmacology · 2020Review
- Separation of Acute Desensitization and Long-Term Tolerance ofMolecular pharmacology · 2019Article
- Dynamic Opioid Receptor Regulation in the Periphery.Molecular pharmacology · 2019Review
- Complex formation between the vasopressin 1b receptor, β-arrestin-2, and the μ-opioid receptor underlies morphine tolerance.Nature neuroscience · 2018Article
- Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via βFrontiers in cellular neuroscience · 2017Article
- Article
- Agonist Binding and Desensitization of the μ-Opioid Receptor Is Modulated by Phosphorylation of the C-Terminal Tail Domain.Molecular pharmacology · 2015Article
- Mu opioid receptor stimulation activates c-Jun N-terminal kinase 2 by distinct arrestin-dependent and independent mechanisms.Cellular signalling · 2015Article
- Role of G Protein-Coupled Receptor Kinases 2 and 3 in μ-Opioid Receptor Desensitization and Internalization.Molecular pharmacology · 2015Article
- Downregulation of Spinal G Protein-Coupled Kinase 2 Abolished the Antiallodynic Effect of Electroacupuncture.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- Morphine-induced internalization of the L83I mutant of the rat μ-opioid receptor.British journal of pharmacology · 2015Article
- The μ-opioid receptor: an electrophysiologist's perspective from the sharp end.British journal of pharmacology · 2015Review
- β-Arrestin-2 knockout prevents development of cellular μ-opioid receptor tolerance but does not affect opioid-withdrawal-related adaptations in single PAG neurons.British journal of pharmacology · 2015Article
- Nerve growth factor induces neurite outgrowth of PC12 cells by promoting Gβγ-microtubule interaction.BMC neuroscience · 2014Article
- β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia.Handbook of experimental pharmacology · 2014Review
- Opioid receptor desensitization: mechanisms and its link to tolerance.Frontiers in pharmacology · 2014Review
- Increased agonist affinity at the μ-opioid receptor induced by prolonged agonist exposure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sustained stimulation of G-protein coupled receptors (GPCRs) leads to rapid loss of receptor function (acute desensitization). For many GPCRs including the mu-opioid receptor (MOR), an accepted mechanism for acute desensitization is through G-protein coupled receptor kinase (GRKs) mediated phosphorylation of the receptor, which facilitates the binding of beta-arrestins (betaarrs) to the receptor and then promotes endocytosis. However, the mechanism(s) that mediate acute desensitization have not yet been well defined in native neurons. This study used whole-cell patch clamp recording of G-protein coupled inward-rectifying potassium (GIRK) currents to assay MOR function and identify mechanisms of acute MOR desensitization in locus ceruleus (LC) neurons. The rate and extent of MOR desensitization were unaffected by beta(arr)-2 knock-out. Disruption of GRK2 function via inhibitory peptide introduced directly into neurons also failed to affect desensitization in wild type or beta(arr)-2 knock-outs. Inhibition of ERK1/2 activation alone had little effect on acute desensitization. However, when both GRK2-beta(arr)-2 and ERK1/2 functions were disrupted simultaneously, desensitization of MOR was nearly abolished. Together, these results suggest that acute desensitization of MOR in native LC neurons is determined by at least two molecular pathways, one involving GRK2 and beta(arr)2, and a parallel pathway mediated by activated ERK1/2.
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