ArticleCell reports2016
GRK2 Constitutively Governs Peripheral Delta Opioid Receptor Activity.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed.
- Lymphotoxin-beta receptor controls the development of chronic pain.Cell reports · 2026Article
- Neuronal cells' calcium influx modulates in response to 940 nm laser irradiation.Lasers in medical science · 2025Article
- Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.Brain, behavior, and immunity · 2025Article
- Molecular and Epigenetic Aspects of Opioid Receptors in Drug Addiction and Pain Management in Sport.International journal of molecular sciences · 2023Review
- Distribution of delta and mu opioid receptor mRNA in rodent dorsal root ganglia neurons.The European journal of neuroscience · 2022Article
- Raf kinase inhibitory protein reduces bradykinin receptor desensitization.Journal of neurochemistry · 2022Article
- Review
- Exploiting Injury-Induced Peripheral Opioid Receptor Changes in Novel Analgesic Development for Chronic Pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Delta opioid receptor activation modulates affective pain and modality-specific pain hypersensitivity associated with chronic neuropathic pain.Journal of neuroscience research · 2022Article
- Article
- Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021Article
- GRK2 Dictates a Functional Switch of the Peripheral Mu-Opioid Receptor.ACS chemical neuroscience · 2020Article
- Post-translational Modifications of Opioid Receptors.Trends in neurosciences · 2020Review
- Alleviating pain with delta opioid receptor agonists: evidence from experimental models.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Dual-Acting Peripherally Restricted Delta/Kappa Opioid (CAV1001) Produces Antinociception in Animal Models of Sub-Acute and Chronic Pain.Journal of pain research · 2020Article
- Dynamic Opioid Receptor Regulation in the Periphery.Molecular pharmacology · 2019Review
- Exploring Morphine-Triggered PKC-Targets and Their Interaction with Signaling Pathways Leading to Pain via TrkA.Proteomes · 2018Review
- Serum response factor mediates nociceptor inflammatory pain plasticity.Pain reports · 2018Article
- Delta Opioid Receptor Expression and Function in Primary Afferent Somatosensory Neurons.Handbook of experimental pharmacology · 2018Review
- PI3K class II α regulates δ-opioid receptor export from theMolecular biology of the cell · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Opioids remain the standard for analgesic care; however, adverse effects of systemic treatments contraindicate long-term administration. While most clinical opioids target mu opioid receptors (MOR), those that target the delta class (DOR) also demonstrate analgesic efficacy. Furthermore, peripherally restrictive opioids represent an attractive direction for analgesia. However, opioid receptors including DOR are analgesically incompetent in the absence of inflammation. Here, we report that G protein-coupled receptor kinase 2 (GRK2) naively associates with plasma membrane DOR in peripheral sensory neurons to inhibit analgesic agonist efficacy. This interaction prevents optimal Gβ subunit association with the receptor, thereby reducing DOR activity. Importantly, bradykinin stimulates GRK2 movement away from DOR and onto Raf kinase inhibitory protein (RKIP). protein kinase C (PKC)-dependent RKIP phosphorylation induces GRK2 sequestration, restoring DOR functionality in sensory neurons. Together, these results expand the known function of GRK2, identifying a non-internalizing role to maintain peripheral DOR in an analgesically incompetent state.
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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.