ArticleOncotarget2015
The ON:OFF switch, σ1R-HINT1 protein, controls GPCR-NMDA receptor cross-regulation: implications in neurological disorders.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- The influence of HINT1 protein in nucleus accumbens on aggressive behavior and anxiety-like behavior.Psychopharmacology · 2026Article
- The SigmaPharmacological reports : PR · 2026Article
- Targeting HINT1 to improve synaptic plasticity: toward loganin as a new antidepressant strategy.Molecular psychiatry · 2025Article
- The Many Faces of Histidine Triad Nucleotide Binding Protein 1 (HINT1).ACS pharmacology & translational science · 2023Review
- Sigma-1 receptor and seizures.Pharmacological research · 2023Review
- Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity.Pharmaceutics · 2023Article
- CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity.Frontiers in pharmacology · 2023Article
- Article
- Veratramine ameliorates pain symptoms in rats with diabetic peripheral neuropathy by inhibiting activation of the SIGMAR1-NMDAR pathway.Pharmaceutical biology · 2022Article
- HINT1 neuropathy in Lithuania: clinical, genetic, and functional profiling.Orphanet journal of rare diseases · 2022Article
- Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders.Neuroscience and biobehavioral reviews · 2022Review
- The σ1 Receptor and the HINT1 Protein Control α2δ1 Binding to Glutamate NMDA Receptors: Implications in Neuropathic Pain.Biomolecules · 2021Article
- The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets.International journal of molecular sciences · 2021Review
- Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins.Molecular neurobiology · 2021Article
- HINT1 neuropathy in Norway: clinical, genetic and functional profiling.Orphanet journal of rare diseases · 2021Article
- Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue.International journal of molecular sciences · 2020Article
- The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception.Molecular brain · 2020Article
- The ALS-related σ1R E102Q Mutant Eludes Ligand Control and Exhibits Anomalous Response to Calcium.International journal of molecular sciences · 2020Article
- The role of HINT1 in methamphetamine-induced behavioral sensitization.Psychopharmacology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the brain, the histidine triad nucleotide-binding protein 1 (HINT1) and sigma 1 receptors (σ1Rs) coordinate the activity of certain G-protein coupled receptors (GPCRs) with that of glutamate N-methyl-D-aspartate receptors (NMDARs). To determine the role of HINT1-σ1R in the plasticity of GPCR-NMDAR interactions, substances acting at MOR, cannabinoid CB1 receptor, NMDAR and σ1R were injected into mice, and their effects were evaluated through in vivo, ex vivo, and in vitro assays. It was observed that HINT1 protein binds to GPCRs and NMDAR NR1 subunits in a calcium-independent manner, whereas σ1R binding to these proteins increases in the presence of calcium. In this scenario, σ1R agonists keep HINT1 at the GPCR and stimulate GPCR-NMDAR interaction, whereas σ1R antagonists transfer HINT1 to NR1 subunits and disengage both receptors. This regulation is lost in σ1R-/- mice, where HINT1 proteins mostly associate with NMDARs, and GPCRs are physically and functionally disconnected from NMDARs. In HINT1-/- mice, ischemia produces low NMDAR-mediated brain damage, suggesting that several different GPCRs enhance glutamate excitotoxicity via HINT1-σ1R. Thus, several GPCRs associate with NMDARs by a dynamic process under the physiological control of HINT1 proteins and σ1Rs. The NMDAR-HINT1-σ1R complex deserves attention because it offers new therapeutic opportunities.
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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.