ReviewMolecular neurobiology2013
Nitric oxide and zinc-mediated protein assemblies involved in mu opioid receptor signaling.
Review in Molecular neurobiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 46 citations in OpenAlex.
- Metal coordination at biological interfaces: Mechanisms, therapeutics, and translation.Materials today. Bio · 2026Review
- A new paradigm in Parkinson's disease: kidney-origin α-synuclein pathology driven by PKC signaling and aurothioglucose.Inflammopharmacology · 2026Review
- Article
- The Endolysosomal Transporter DMT1 is Required for Morphine Regulation of Neuronal Ferritin Heavy Chain.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- The ventilatory depressant actions but not the antinociceptive effects of morphine are blunted in rats receiving intravenous infusion of L-cysteine ethyl ester.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- S-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Nitrosyl factors play a vital role in the ventilatory depressant effects of fentanyl in unanesthetized rats.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- S-Nitroso-L-Cysteine Stereoselectively Blunts the Deleterious Effects of Fentanyl on Breathing While Augmenting Antinociception in Freely-Moving Rats.Frontiers in pharmacology · 2022Article
- The σ1 Receptor and the HINT1 Protein Control α2δ1 Binding to Glutamate NMDA Receptors: Implications in Neuropathic Pain.Biomolecules · 2021Article
- Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?Cellular and molecular neurobiology · 2021Review
- Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins.Molecular neurobiology · 2021Article
- Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue.International journal of molecular sciences · 2020Article
- The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease.Antioxidants & redox signaling · 2019Article
- Ligands Exert Biased Activity to Regulate Sigma 1 Receptor Interactions With Cationic TRPA1, TRPV1, and TRPM8 Channels.Frontiers in pharmacology · 2019Article
- The Plasma Membrane: A Platform for Intra- and Intercellular Redox Signaling.Antioxidants (Basel, Switzerland) · 2018Review
- Metaplasticity in the Visual Cortex: Crosstalk Between Visual Experience and Reactive Oxygen Species.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Increased PKC activity and altered GSK3β/NMDAR function drive behavior cycling in HINT1-deficient mice: bipolarity or opposing forces.Scientific reports · 2017Article
- Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats.The Journal of pharmacology and experimental therapeutics · 2016Article
- Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction.Oncotarget · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Opioids are among the most effective analgesics in controlling the perception of intense pain, although their continuous use decreases their potency due to the development of tolerance. The glutamate N-methyl-D-aspartate (NMDA) receptor system is currently considered to be the most relevant functional antagonist of morphine analgesia. In the postsynapse of different brain regions the C terminus of the mu-opioid receptor (MOR) associates with NR1 subunits of NMDARs, as well as with a series of signaling proteins, such as neural nitric oxide synthase (nNOS)/nitric oxide (NO), protein kinase C (PKC), calcium and calmodulin-dependent kinase II (CaMKII) and the mitogen-activated protein kinases (MAPKs). NO is implicated in redox signaling and PKC falls under the regulation of zinc metabolism, suggesting that these signaling elements might participate in the regulation of MOR activity by the NMDAR. In this review, we discuss the influence of redox signaling in the mechanisms whose plasticity triggers opioid tolerance. Thus, the MOR C terminus assembles a series of signaling proteins around the homodimeric histidine triad nucleotide-binding protein 1 (HINT1). The NMDAR NR1 subunit and the regulator of G protein signaling RGSZ2 bind HINT1 in a zinc-independent manner, with RGSZ2 associating with nNOS and regulating MOR-induced production of NO. This NO acts on the RGSZ2 zinc finger, providing the zinc ions that are required for PKC/Raf-1 cysteine-rich domains to simultaneously bind to the histidines present in the HINT1 homodimer. The MOR-induced activation of phospholipase β (PLCβ) regulates PKC, which increases the reactive oxygen species (ROS) by acting on NOX/NADPH, consolidating the long-term PKC activation required to regulate the Raf-1/MAPK cascade and enhancing NMDAR function. Thus, RGSZ2 serves as a Redox Zinc Switch that converts NO signals into Zinc signals, thereby modulating Redox Sensor Proteins like PKCγ and Raf-1. Accordingly, redox-dependent and independent processes weave together to situate the MOR under the negative control of the NMDAR.
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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.