ArticleThe Journal of biological chemistry2012
Serine 363 is required for nociceptin/orphanin FQ opioid receptor (NOPR) desensitization, internalization, and arrestin signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- G Protein-Coupled Receptor Kinase 5 (GRK5) Modulates Nociceptin/Orphanin FQ Opioid (NOP) Receptor Desensitization in Rat Sympathetic Neurons.Journal of neuroscience research · 2026Article
- Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system.Cell reports · 2025Article
- Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.Nature communications · 2024Article
- Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.bioRxiv : the preprint server for biology · 2024Article
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain.Molecules (Basel, Switzerland) · 2022Review
- Therapeutic potentials of NOP and MOP receptor coactivation for the treatment of pain and opioid abuse.Journal of neuroscience research · 2022Review
- Differential In Vitro Pharmacological Profiles of Structurally Diverse Nociceptin Receptor Agonists in Activating G Protein and Beta-Arrestin Signaling at the Human Nociceptin Opioid Receptor.Molecular pharmacology · 2021Article
- Adaptive Changes in the Central Control of Energy Homeostasis Occur in Response to Variations in Energy Status.International journal of molecular sciences · 2021Review
- Functional Selectivity Does Not Predict Antinociceptive/Locomotor Impairing Potencies of NOP Receptor Agonists.Frontiers in neuroscience · 2021Article
- Review
- Biased Opioid Ligands.Molecules (Basel, Switzerland) · 2020Review
- Post-translational Modifications of Opioid Receptors.Trends in neurosciences · 2020Review
- Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists.Science signaling · 2019Article
- Nociceptin Receptor Is Overexpressed in Non-small Cell Lung Cancer and Predicts Poor Prognosis.Frontiers in oncology · 2019Article
- The standardized Withania somnifera Dunal root extract alters basal and morphine-induced opioid receptor gene expression changes in neuroblastoma cells.BMC complementary and alternative medicine · 2018Article
- Beta-arrestin 2 rather than G protein efficacy determines the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands.Neuropharmacology · 2016Article
- Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems.Pharmacological reviews · 2016Review
- Convergent phosphomodulation of the major neuronal dendritic potassium channel Kv4.2 by pituitary adenylate cyclase-activating polypeptide.Neuropharmacology · 2016Article
- Optodynamic simulation of β-adrenergic receptor signalling.Nature communications · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
We determined the role of carboxyl-terminal regulation of NOPR (nociceptin, orphanin FQ receptor) signaling and function. We mutated C-terminal serine and threonine residues and examined their role in NOPR trafficking, homologous desensitization, and arrestin-dependent MAPK signaling. The NOPR agonist, nociceptin, caused robust NOPR-YFP receptor internalization, peaking at 30 min. Mutation of serine 337, 346, and 351, had no effect on NOPR internalization. However, mutation of C-terminal threonine 362, serine 363, and threonine 365 blocked nociceptin-induced internalization of NOPR. Furthermore, point mutation of only Ser-363 was sufficient to block NOPR internalization. Homologous desensitization of NOPR-mediated calcium channel blockade and inhibition of cAMP were also shown to require Ser-363. Additionally, NOPR internalization was absent when GRK3, and Arrestin3 were knocked down using siRNA, but not when GRK2 and Arrestin2 were knocked down. We also found that nociceptin-induced NOPR-mediated JNK but not ERK signaling requires Ser-363, GRK3, and Arrestin3. Dominant-positive Arrestin3 but not Arrestin2 was sufficient to rescue NOPR-S363A internalization and JNK signaling. These findings suggest that NOPR function may be regulated by GRK3 phosphorylation of Ser-363 and Arrestin3 and further demonstrates the complex nature of G-protein-dependent and -independent signaling in opioid receptors.
Indexed as
Identifiers
What OpenQuestion holds
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.