ArticleBiophysical journal2017
Sites Contributing to TRPA1 Activation by the Anesthetic Propofol Identified by Photoaffinity Labeling.
Article in Biophysical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- [Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial].Brazilian journal of anesthesiology (Elsevier)Trial
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Propofol reduces human TRPA1 activity in a warm environment.Biochemistry and biophysics reports · 2025Article
- CYP1B1-derived epoxides modulate the TRPA1 channel in chronic pain.Acta pharmaceutica Sinica. B · 2023Article
- TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels.Current issues in molecular biology · 2022Article
- Binding Sites and the Mechanism of Action of Propofol and a Photoreactive Analogue in Prokaryotic Voltage-Gated Sodium Channels.ACS chemical neuroscience · 2021Article
- Structural Pharmacology of TRP Channels.Journal of molecular biology · 2021Review
- Transient Receptor Potential Channel Ankyrin 1: A Unique Regulator of Vascular Function.Cells · 2021Review
- Inhibition of Ligand-Gated TRPA1 by General Anesthetics.Molecular pharmacology · 2020Article
- Article
- Regulation of vascular tone by transient receptor potential ankyrin 1 channels.Current topics in membranes · 2020Review
- TRPA1 modulation by piperidine carboxamides suggests an evolutionarily conserved binding site and gating mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Azi-medetomidine: Synthesis and Characterization of a Novel α2 Adrenergic Photoaffinity Ligand.ACS chemical neuroscience · 2019Article
- Computational Drug Repurposing Algorithm Targeting TRPA1 Calcium Channel as a Potential Therapeutic Solution for Multiple Sclerosis.Pharmaceutics · 2019Article
- Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery.Trends in pharmacological sciences · 2019Review
- Alkylphenol inverse agonists of HCN1 gating: H-bond propensity, ring saturation and adduct geometry differentially determine efficacy and potency.Biochemical pharmacology · 2019Article
- The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges.Frontiers in pharmacology · 2019Review
- Propofol inhibits prokaryotic voltage-gated NaThe Journal of general physiology · 2018Article
- Recent progress on the molecular pharmacology of propofol.F1000Research · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
In addition to inducing anesthesia, propofol activates a key component of the pain pathway, the transient receptor potential ankyrin 1 ion channel (TRPA1). Recent mutagenesis studies suggested a potential activation site within the transmembrane domain, near the A-967079 cavity. However, mutagenesis cannot distinguish between protein-based and ligand-based mechanisms, nor can this site explain the complex modulation by propofol. Thus more direct approaches are required to reveal potentially druggable binding sites. Here we apply photoaffinity labeling using a propofol derivative, meta-azipropofol, for direct identification of binding sites in mouse TRPA1. We confirm that meta-azipropofol activates TRPA1 like the parent anesthetic, and identify two photolabeled residues (V954 and E969) in the S6 helix. In combination with docking to closed and open state models of TRPA1, photoaffinity labeling suggested that the A-967079 cavity is a positive modulatory site for propofol. Further, the photoaffinity labeling of E969 indicated pore block as a likely mechanism for propofol inhibition at high concentrations. The direct identification of drug-binding sites clarifies the molecular mechanisms of important TRPA1 agonists, and will facilitate drug design efforts to modulate TRPA1.
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What OpenQuestion holds
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.