ArticleThe Journal of biological chemistry2011
Modulating micro-opioid receptor phosphorylation switches agonist-dependent signaling as reflected in PKCepsilon activation and dendritic spine stability.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Oxycodone in the Opioid Epidemic: High 'Liking', 'Wanting', and Abuse Liability.Cellular and molecular neurobiology · 2021Review
- Recent Insights from Molecular Dynamics Simulations for G Protein-Coupled Receptor Drug Discovery.International journal of molecular sciences · 2019Review
- Decreased Level of Blood MicroRNA-133b in Men with Opioid Use Disorder on Methadone Maintenance Therapy.Journal of clinical medicine · 2019Article
- Molecular dynamics of fentanyl bound to μ-opioid receptor.Journal of molecular modeling · 2019Article
- Activation of the G Protein-Coupled Estrogen Receptor Elicits Store Calcium Release and Phosphorylation of the Mu-Opioid Receptors in the Human Neuroblastoma SH-SY5Y Cells.Frontiers in neuroscience · 2019Article
- Novel Roles of Non-Coding RNAs in Opioid Signaling and Cardioprotection.Non-coding RNA · 2018Review
- Spinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.Pharmacological research · 2017Article
- Functional Selectivity of CB2 Cannabinoid Receptor Ligands at a Canonical and Noncanonical Pathway.The Journal of pharmacology and experimental therapeutics · 2016Article
- Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.Lipids in health and disease · 2016Article
- Ligand-biased activation of extracellular signal-regulated kinase 1/2 leads to differences in opioid induced antinociception and tolerance.Behavioural brain research · 2016Article
- Functional selectivity and time-dependence of μ-opioid receptor desensitization at nerve terminals in the mouse ventral tegmental area.British journal of pharmacology · 2015Article
- Ligand requirements for involvement of PKCε in synergistic analgesic interactions between spinal μ and δ opioid receptors.British journal of pharmacology · 2015Article
- Neurod1 modulates opioid antinociceptive tolerance via two distinct mechanisms.Biological psychiatry · 2014Article
- Morphine-induced trafficking of a mu-opioid receptor interacting protein in rat locus coeruleus neurons.Progress in neuro-psychopharmacology & biological psychiatry · 2014Article
- FK506-binding protein 12 modulates μ-opioid receptor phosphorylation and protein kinase C(ε)-dependent signaling by its direct interaction with the receptor.Molecular pharmacology · 2014Article
- Opioid receptor desensitization: mechanisms and its link to tolerance.Frontiers in pharmacology · 2014Review
- Analgesic tolerance of opioid agonists in mutant mu-opioid receptors expressed in sensory neurons following intrathecal plasmid gene delivery.Molecular pain · 2013Article
- Opioid receptors: toward separation of analgesic from undesirable effects.Trends in biochemical sciences · 2013Review
- Opioid receptor interacting proteins and the control of opioid signaling.Current pharmaceutical design · 2013Review
- Posttranslation modification of G protein-coupled receptor in relationship to biased agonism.Methods in enzymology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
A new role of G protein-coupled receptor (GPCR) phosphorylation was demonstrated in the current studies by using the μ-opioid receptor (OPRM1) as a model. Morphine induces a low level of receptor phosphorylation and uses the PKCε pathway to induce ERK phosphorylation and receptor desensitization, whereas etorphine, fentanyl, and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) induce extensive receptor phosphorylation and use the β-arrestin2 pathway. Blocking OPRM1 phosphorylation (by mutating Ser363, Thr370 and Ser375 to Ala) enabled etorphine, fentanyl, and DAMGO to use the PKCε pathway. This was not due to the decreased recruitment of β-arrestin2 to the receptor signaling complex, because these agonists were unable to use the PKCε pathway when β-arrestin2 was absent. In addition, overexpressing G protein-coupled receptor kinase 2 (GRK2) decreased the ability of morphine to activate PKCε, whereas overexpressing dominant-negative GRK2 enabled etorphine, fentanyl, and DAMGO to activate PKCε. Furthermore, by overexpressing wild-type OPRM1 and a phosphorylation-deficient mutant in primary cultures of hippocampal neurons, we demonstrated that receptor phosphorylation contributes to the differential effects of agonists on dendritic spine stability. Phosphorylation blockage made etorphine, fentanyl, and DAMGO function as morphine in the primary cultures. Therefore, agonist-dependent phosphorylation of GPCR regulates the activation of the PKC pathway and the subsequent responses.
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Registered trials
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