ArticleCellular signalling2010
Agonist-dependent mu-opioid receptor signaling can lead to heterologous desensitization.
Article in Cellular signalling, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Pooled it
- Phosphovariants of the canonical heterotrimeric Gα protein, GPA1, differentially affect G protein activity and Arabidopsis development.bioRxiv : the preprint server for biology · 2026Article
- Growth factor-dependent phosphorylation of GαScience signaling · 2024Article
- Oxycodone in the Opioid Epidemic: High 'Liking', 'Wanting', and Abuse Liability.Cellular and molecular neurobiology · 2021Review
- Chronic Treatment with Morphine Disrupts Acute Kinase-Dependent Desensitization of GPCRs.Molecular pharmacology · 2020Article
- GαExperimental & molecular medicine · 2020Review
- A cellular perspective of bias at G protein-coupled receptors.Protein science : a publication of the Protein Society · 2020Review
- Post-translational Modifications of Opioid Receptors.Trends in neurosciences · 2020Review
- Article
- cAMP guided his way: a life for G protein-mediated signal transduction and molecular pharmacology-tribute to Karl H. Jakobs.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- CB1 cannabinoid receptor-phosphorylated fourth intracellular loop structure-function relationships.Peptide science (Hoboken, N.J.) · 2019Article
- Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects.Nature communications · 2019Article
- Presynaptic mGluRs Control the Duration of Endocannabinoid-Mediated DSI.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- G protein subunit phosphorylation as a regulatory mechanism in heterotrimeric G protein signaling in mammals, yeast, and plants.The Biochemical journal · 2018Review
- Exchange factor directly activated by cAMP-PKCε signalling mediates chronic morphine-induced expression of purine P2X3 receptor in rat dorsal root ganglia.British journal of pharmacology · 2018Article
- Article
- 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 combined inhibitory effect of the adenosine A1 and cannabinoid CB1 receptors on cAMP accumulation in the hippocampus is additive and independent of A1 receptor desensitization.BioMed research international · 2015Article
- Role of FK506 binding protein 12 in morphine-induced μ-opioid receptor internalization and desensitization.Neuroscience letters · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Desensitization of the micro-opioid receptor (MOR) has been implicated as an important regulatory process in the development of tolerance to opiates. Monitoring the release of intracellular Ca(2+) ([Ca(2+)](i)), we reported that [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO)-induced receptor desensitization requires receptor phosphorylation and recruitment of beta-arrestins (betaArrs), while morphine-induced receptor desensitization does not. In current studies, we established that morphine-induced MOR desensitization is protein kinase C (PKC)-dependent. By using RNA interference techniques and subtype specific inhibitors, PKCepsilon was shown to be the PKC subtype activated by morphine and the subtype responsible for morphine-induced desensitization. In contrast, DAMGO did not increase PKCepsilon activity and DAMGO-induced MOR desensitization was not affected by modulating PKCepsilon activity. Among the various proteins within the receptor signaling complex, Galphai2 was phosphorylated by morphine-activated PKCepsilon. Moreover, mutating three putative PKC phosphorylation sites, Ser(44), Ser(144) and Ser(302) on Galphai2 to Ala attenuated morphine-induced, but not DAMGO-induced desensitization. In addition, pretreatment with morphine desensitized cannabinoid receptor CB1 agonist WIN 55212-2-induced [Ca(2+)](i) release, and this desensitization could be reversed by pretreating the cells with PKCepsilon inhibitor or overexpressing Galphai2 with the putative PKC phosphorylation sites mutated. Thus, depending on the agonist, activation of MOR could lead to heterologous desensitization and probable crosstalk between MOR and other Galphai-coupled receptors, such as the CB1.
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Registered trials
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