ArticleThe Journal of biological chemistry2013
Identification of propofol binding sites in a nicotinic acetylcholine receptor with a photoreactive propofol analog.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Delayed presentation of breast cancer patients and contributing factors in East Africa: Systematic review and meta-analysis.PloS one · 2024Pooled it
- Neuro-Transcriptomic Responses to Polypharmacological Agents inBrain sciences · 2026Article
- Article
- Identifying c-fos Expression as a Strategy to Investigate the Actions of General Anesthetics on the Central Nervous System.Current neuropharmacology · 2022Review
- Current State of Potential Mechanisms Supporting Low Intensity Focused Ultrasound for Neuromodulation.Frontiers in human neuroscience · 2022Review
- Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels.Frontiers in physiology · 2021Review
- Menthol Binding to the Human α4β2 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane.The journal of physical chemistry. B · 2020Article
- Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery.Trends in pharmacological sciences · 2019Review
- A photoreactive analog of allopregnanolone enables identification of steroid-binding sites in a nicotinic acetylcholine receptor.The Journal of biological chemistry · 2019Article
- Binding of the general anesthetic sevoflurane to ion channels.PLoS computational biology · 2018Article
- Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Propofol inhibits prokaryotic voltage-gated NaThe Journal of general physiology · 2018Article
- Current advances of carbene-mediated photoaffinity labeling in medicinal chemistry.RSC advances · 2018Review
- Nicotinic acetylcholine receptors at the single-channel level.British journal of pharmacology · 2018Review
- Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.Biochimica et biophysica acta. Biomembranes · 2018Review
- X-Ray Crystallographic Studies for Revealing Binding Sites of General Anesthetics in Pentameric Ligand-Gated Ion Channels.Methods in enzymology · 2018Article
- Recent progress on the molecular pharmacology of propofol.F1000Research · 2018Review
- Intravenous Anesthetic Protects Hepatocyte from Reactive Oxygen Species-Induced Cellular Apoptosis during Liver TransplantationOxidative medicine and cellular longevity · 2018Article
- Enantiomeric barbiturates bind distinct inter- and intrasubunit binding sites in a nicotinic acetylcholine receptor (nAChR).The Journal of biological chemistry · 2017Article
- Synthesis and pharmacological evaluation of neurosteroid photoaffinity ligands.European journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Propofol, a widely used intravenous general anesthetic, acts at anesthetic concentrations as a positive allosteric modulator of γ-aminobutyric acid type A receptors and at higher concentration as an inhibitor of nicotinic acetylcholine receptors (nAChRs). Here, we characterize propofol binding sites in a muscle-type nAChR by use of a photoreactive analog of propofol, 2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol (AziPm). Based upon radioligand binding assays, AziPm stabilized the Torpedo nAChR in the resting state, whereas propofol stabilized the desensitized state. nAChR-rich membranes were photolabeled with [(3)H]AziPm, and labeled amino acids were identified by Edman degradation. [(3)H]AziPm binds at three sites within the nAChR transmembrane domain: (i) an intrasubunit site in the δ subunit helix bundle, photolabeling in the nAChR desensitized state (+agonist) δM2-18' and two residues in δM1 (δPhe-232 and δCys-236); (ii) in the ion channel, photolabeling in the nAChR resting, closed channel state (-agonist) amino acids in the M2 helices (αM2-6', βM2-6' and -13', and δM2-13') that line the channel lumen (with photolabeling reduced by >90% in the desensitized state); and (iii) at the γ-α interface, photolabeling αM2-10'. Propofol enhanced [(3)H]AziPm photolabeling at αM2-10'. Propofol inhibited [(3)H]AziPm photolabeling within the δ subunit helix bundle at lower concentrations (IC50 = 40 μm) than it inhibited ion channel photolabeling (IC50 = 125 μm). These results identify for the first time a single intrasubunit propofol binding site in the nAChR transmembrane domain and suggest that this is the functionally relevant inhibitory binding site.
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