ArticleMolecular pharmacology2009
Time-resolved photolabeling of the nicotinic acetylcholine receptor by [3H]azietomidate, an open-state inhibitor.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Structural interplay of anesthetics and paralytics on muscle nicotinic receptors.Nature communications · 2023Article
- Menthol Binding to the Human α4β2 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane.The journal of physical chemistry. B · 2020Article
- Recent progress on the molecular pharmacology of propofol.F1000Research · 2018Review
- Shedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands.Anesthesia and analgesia · 2016Review
- Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels.Anesthesiology · 2016Article
- Structural Studies of GABAA Receptor Binding Sites: Which Experimental Structure Tells us What?Frontiers in molecular neuroscience · 2016Article
- Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.Scientific reports · 2015Article
- Anesthetics target interfacial transmembrane sites in nicotinic acetylcholine receptors.Neuropharmacology · 2015Review
- Desformylflustrabromine (dFBr) and [3H]dFBr-Labeled Binding Sites in a Nicotinic Acetylcholine Receptor.Molecular pharmacology · 2015Article
- Atomistic insights into human Cys-loop receptors by solution NMR.Biochimica et biophysica acta · 2015Article
- Structural models of ligand-gated ion channels: sites of action for anesthetics and ethanol.Alcoholism, clinical and experimental research · 2014Review
- Mechanisms revealed through general anesthetic photolabeling.Current anesthesiology reports · 2014Article
- Photoaffinity labeling the propofol binding site in GLIC.Biochemistry · 2014Article
- The minimum M3-M4 loop length of neurotransmitter-activated pentameric receptors is critical for the structural integrity of cytoplasmic portals.The Journal of biological chemistry · 2013Article
- NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR.Biochimica et biophysica acta · 2013Article
- Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue.Biochemistry · 2012Article
- Molecular dissection of Cl--selective Cys-loop receptor points to components that are dispensable or essential for channel activity.The Journal of biological chemistry · 2011Article
- Isoflurane alters the structure and dynamics of GLIC.Biophysical journal · 2011Article
- Multiple transmembrane binding sites for p-trifluoromethyldiazirinyl-etomidate, a photoreactive Torpedo nicotinic acetylcholine receptor allosteric inhibitor.The Journal of biological chemistry · 2011Article
- Anesthetic sites and allosteric mechanisms of action on Cys-loop ligand-gated ion channels.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2011Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Azietomidate is a photoreactive analog of the general anesthetic etomidate that acts as a nicotinic acetylcholine receptor (nAChR) noncompetitive antagonist. We used rapid perfusion electrophysiological techniques to characterize the state dependence and kinetics of azietomidate inhibition of Torpedo californica nAChRs and time-resolved photolabeling to identify the nAChR binding sites occupied after exposure to [(3)H]azietomidate and agonist for 50 ms (open state) or at equilibrium (desensitized state). Azietomidate acted primarily as an open channel inhibitor characterized by a bimolecular association rate constant of k(+) = 5 x 10(5) M(-1) s(-1) and a dissociation rate constant of <3s(-1). Azietomidate at 10 microM, when perfused with acetylcholine (ACh), inhibited the ACh response by approximately 50% after 50 ms; when preincubated for 10 s, it decreased the peak initial response by approximately 15%. Comparison of the kinetics of recovery of ACh responses after exposure to ACh and azietomidate or to ACh alone indicated that at subsecond times, azietomidate inhibited nAChRs without enhancing the kinetics of agonist-induced desensitization. In nAChRs frozen after 50-ms exposure to agonist and [(3)H]azietomidate, amino acids were photolabeled in the ion channel [position M2-20 (alphaGlu-262, betaAsp-268, deltaGln-276)], in deltaM1 (deltaCys-236), and in alphaMA/alphaM4 (alphaGlu-390, alphaCys-412) that were also photolabeled in nAChRs in the equilibrium desensitized state at approximately half the efficiency. These results identify azietomidate binding sites at the extracellular end of the ion channel, in the delta subunit helix bundle, and in the nAChR cytoplasmic domain that seem similar in structure and accessibility in the open and desensitized states of the nAChR.
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