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Volatile Anesthetics Bind Rat Synaptic Snare Proteins
Open accessAbstract
Background: Volatile general anesthetics (VAs) have a number of synaptic actions, one of which is to inhibit excitatory neurotransmitter release; however, no presynaptic VA binding proteins have been identified. Genetic data in Caenorhabditis elegans have led to the hypothesis that a protein that interacts with the presynaptic protein syntaxin 1A is a VA target. Motivated by this hypothesis, the authors measured the ability of syntaxin 1A and proteins that interact with syntaxin to bind to halothane and isoflurane. Methods: Recombinant rat syntaxin 1A, SNAP-25B, VAMP2, and the ternary SNARE complex that they form were tested. Binding of VAs to these proteins was detected by F-nuclear magnetic resonance relaxation measurements. Structural alterations in the proteins were examined by circular dichroism and ability to form complexes. Results: Volatile anesthetics did not bind to VAMP2. At concentrations in the clinical range, VAs did bind to SNAP-25B; however, binding was detected only in preparations containing SNAP-25B homomultimers. VAs also bound at clinical concentrations to both syntaxin and the SNARE complex. Addition of an N-terminal His6 tag to syntaxin abolished its ability to bind VAs despite normal secondary structure and ability to form SNARE complexes; thrombin cleavage of the tag restored VA binding. Thus, the VA binding site(s) has structural requirements and is not simply any alpha-helical bundle. VAs at supraclinical concentrations produced an increase in helicity of the SNARE complex; otherwise, VA binding produced no gross alteration in the stability or secondary structure of the SNARE complex. Conclusion: SNARE proteins are potential synaptic targets of volatile anesthetics.
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Volatile anesthetics bind directly to syntaxin and the SNARE complex.
“Volatile anesthetics have been shown to bind directly to syntaxin and the SNARE complex [76, 77].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [76]
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The Biology of General Anesthesia from Paramecium to Primate
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Metadata
- Authors
- Nagele, P., Mendel, J. B., Placzek, W. J., Scott, B. A., d'Avignon, D. A., & Crowder, C. M.
- Affiliations
- Adjunct Instructor, Department of Anesthesiology, Washington University School of Medicine. Attending Anesthesiologist, Department of Anesthesiology and General Intensive Care, Medical University of Vienna.
- Undergraduate Research Assistant.
- Senior Research Technician, Department of Anesthesiology.
- Director High Resolution NMR Facility, Department of Chemistry, Washington University.
- Washington University in St. Louis (US)
- Venue
- Anesthesiology
- Published
- 2005-10-01
- Volume
- 103
- Issue
- 4
- Pages
- 768-778
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W2019651658
- Cited by
- 46
- References
- 34
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 1 · 2015: 2 · 2014: 3 · 2012: 5
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm059781-08)
- National Institute of General Medical Sciences (R01GM-059781)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- volatile anesthetics, SNARE proteins, syntaxin 1A, VAMP2, SNARE complex, halothane, isoflurane, neurotransmitter release inhibition, protein secondary structure, anesthetic binding sites
- MeSH terms
- Animals, Protein Binding, Recombinant Proteins, Anesthetics, Inhalation, SNARE Proteins, Synaptosomal-Associated Protein 25, Syntaxin 1, Vesicle-Associated Membrane Protein 2, Rats
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