ArticleCellular and molecular life sciences : CMLS2011
The histidine triad nucleotide-binding protein 1 supports mu-opioid receptor-glutamate NMDA receptor cross-regulation.
Article in Cellular and molecular life sciences : CMLS, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?The American journal of psychiatry · 2025Review
- The Many Faces of Histidine Triad Nucleotide Binding Protein 1 (HINT1).ACS pharmacology & translational science · 2023Review
- Article
- The σ1 Receptor and the HINT1 Protein Control α2δ1 Binding to Glutamate NMDA Receptors: Implications in Neuropathic Pain.Biomolecules · 2021Article
- Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins.Molecular neurobiology · 2021Article
- Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue.International journal of molecular sciences · 2020Article
- The role of HINT1 in methamphetamine-induced behavioral sensitization.Psychopharmacology · 2020Article
- Reply to Hashimoto: Ketamine is not an opioid but requires opioid system for antidepressant actions.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease.Antioxidants & redox signaling · 2019Article
- Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors.Oncotarget · 2018Article
- The Role of HINT1 in Methamphetamine-Induced Conditioned Place Preference.Neurotoxicity research · 2018Article
- Mechanisms of μ-opioid receptor inhibition of NMDA receptor-induced substance P release in the rat spinal cord.Neuropharmacology · 2018Article
- Axonal neuropathy with neuromyotonia: there is a HINT.Brain : a journal of neurology · 2017Review
- Increased PKC activity and altered GSK3β/NMDAR function drive behavior cycling in HINT1-deficient mice: bipolarity or opposing forces.Scientific reports · 2017Article
- 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
- Design, Synthesis, and Characterization of Sulfamide and Sulfamate Nucleotidomimetic Inhibitors of hHint1.ACS medicinal chemistry letters · 2016Article
- Hint1 gene deficiency enhances the supraspinal nociceptive sensitivity in mice.Brain and behavior · 2016Article
- The ON:OFF switch, σ1R-HINT1 protein, controls GPCR-NMDA receptor cross-regulation: implications in neurological disorders.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR. These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein 1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism. Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength. Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms independent of 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.