ArticleNature neuroscience2018
Complex formation between the vasopressin 1b receptor, β-arrestin-2, and the μ-opioid receptor underlies morphine tolerance.
Article in Nature neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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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
20 citing papers in PubMed, 41 citations in OpenAlex.
- Comparison of Oliceridine and Morphine in Postoperative Analgesia in Laparoscopic Total Hysterectomy, a Randomized Double-Blind Controlled Trial.Drug design, development and therapy · 2025Trial
- OPRM1/MRGPRX1 heterodimers drive opioid-induced itch through a peripheral mechanism.Journal of biomedical science · 2026Article
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- FLT3 signaling inhibition abrogates opioid tolerance and hyperalgesia while preserving analgesia.Nature communications · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- The left-right side-specific endocrine signaling in the effects of brain lesions: questioning of the neurological dogma.Cellular and molecular life sciences : CMLS · 2022Review
- Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor.MedComm · 2022Review
- Oxytocin and vasopressin: Signalling, behavioural modulation and potential therapeutic effects.British journal of pharmacology · 2022Review
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Dysregulation of Vesicular Glutamate Transporter VGluT2Frontiers in pharmacology · 2022Article
- Article
- Agonist dependency of the second phase access of β-arrestin 2 to the heteromeric µ-V1b receptor.Scientific reports · 2021Article
- Reduction of prefrontal purinergic signaling is necessary for the analgesic effect of morphine.iScience · 2021Article
- Chronic developmental lead exposure increases μ-opiate receptor levels in the adolescent rat brain.Neurotoxicology · 2021Article
- Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective.Frontiers in pharmacology · 2020Review
- I8-arachnotocin-an arthropod-derived G protein-biased ligand of the human vasopressin VScientific reports · 2019Article
- Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs.Molecular brain · 2019Article
- Arrestin recruitment and signaling by G protein-coupled receptor heteromers.Neuropharmacology · 2019Review
- Heteromerization Modulates mu Opioid Receptor Functional PropertiesFrontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic morphine exposure upregulates adenylate cyclase signaling and reduces analgesic efficacy, a condition known as opioid tolerance. Nonopioid neurotransmitters can enhance morphine tolerance, but the mechanism for this is poorly understood. We show that morphine tolerance was delayed in mice lacking vasopressin 1b receptors (V1bRs) or after administration of V1bR antagonist into the rostral ventromedial medulla, where transcripts for V1bRs and μ-opioid receptors are co-localized. Vasopressin increased morphine-binding affinity in cells expressing both V1bR and μ-opioid receptors. Complex formation among V1bR, β-arrestin-2, and μ-opioid receptor resulted in vasopressin-mediated upregulation of ERK phosphorylation and adenylate cyclase sensitization. A leucine-rich segment in the V1bR C-terminus was necessary for the association with β-arrestin-2. Deletion of this leucine-rich segment increased morphine analgesia and reduced vasopressin-mediated adenylate cyclase sensitization. These findings indicate that inhibition of μ-opioid-receptor-associated V1bR provides an approach for enhancing morphine analgesia without increasing analgesic tolerance.
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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.