ArticleAntioxidants & redox signaling2011
NO-released zinc supports the simultaneous binding of Raf-1 and PKCγ cysteine-rich domains to HINT1 protein at the mu-opioid receptor.
Article in Antioxidants & redox signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- A new paradigm in Parkinson's disease: kidney-origin α-synuclein pathology driven by PKC signaling and aurothioglucose.Inflammopharmacology · 2026Review
- The Many Faces of Histidine Triad Nucleotide Binding Protein 1 (HINT1).ACS pharmacology & translational science · 2023Review
- 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
- Nitrosyl factors play a vital role in the ventilatory depressant effects of fentanyl in unanesthetized rats.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Magnesium and Morphine in the Treatment of Chronic Neuropathic Pain-A Biomedical Mechanism of Action.International journal of molecular sciences · 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
- Depolarization-Dependent C-Raf Signaling Promotes Hyperexcitability and Reduces Opioid Sensitivity of Isolated Nociceptors after Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease.Antioxidants & redox signaling · 2019Article
- HINT1 in Neuropsychiatric Diseases: A Potential Neuroplastic Mediator.Neural plasticity · 2017Review
- Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction.Oncotarget · 2016Review
- Reactive Oxygen-Related Diseases: Therapeutic Targets and Emerging Clinical Indications.Antioxidants & redox signaling · 2015Review
- The σ1 receptor engages the redox-regulated HINT1 protein to bring opioid analgesia under NMDA receptor negative control.Antioxidants & redox signaling · 2015Article
- Nitric oxide and zinc-mediated protein assemblies involved in mu opioid receptor signaling.Molecular neurobiology · 2013Review
- HINT1 protein cooperates with cannabinoid 1 receptor to negatively regulate glutamate NMDA receptor activity.Molecular brain · 2013Article
- The mu-opioid receptor and the NMDA receptor associate in PAG neurons: implications in pain control.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
- Involvement of NOX1/NADPH oxidase in morphine-induced analgesia and tolerance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the brain, the mu-opioid receptor (MOR) activates neural nitric oxide synthase (nNOS) through the PI3K/Akt pathway. The resulting nitric oxide (NO) enhances the function of the glutamate N-methyl-d-aspartate receptor (NMDAR)/calcium and calmodulin-dependent serine/threonine kinase (CaMKII), which subsequently diminishes MOR signaling strength. Because the ERK1/2 cascade is implicated in opioid tolerance, we analyzed the role of morphine-generated NO in this negative regulation. We found that NO-released endogenous zinc ions recruit the Ras/Raf-1/ERK1/2 cassette to histidine triad nucleotide-binding protein 1 (HINT1). A-Raf and B-Raf showed little or no MOR association. The zinc ions bridge the Raf-1 cysteine-rich domain (CRD) with HINT1 at the MOR C-terminus. Morphine also recruits PKCγ via NO/zinc to the MOR-HINT1 complex. Both Raf-1 and PKCγ CRDs bind simultaneously to HINT1, enabling PKCγ to enhance Raf-1 function to intensify MEK/ERK1/2 activation. Thus, through attached HINT1, the MOR facilitates the cross-talk of two NO- and zinc-regulated signal-transduction pathways, PKC/Src and Raf-1/ERK1/2, implicated in the negative control of morphine effects. This study reveals new aspects of ERK1/2 regulation by the MOR without requiring the transactivation of a receptor tyrosine kinase.
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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.