ArticleThe Journal of biological chemistry2014
Molecular basis determining inhibition/activation of nociceptive receptor TRPA1 protein: a single amino acid dictates species-specific actions of the most potent mammalian TRPA1 antagonist.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- TRPA1 for Butterfly Eyespot Formation.International journal of molecular sciences · 2026Article
- TRP Channels from Sensory Coding to Physiology.Metabolites · 2025Review
- Evolutionary adaptations of TRPA1 thermosensitivity and skin thermoregulation in vertebrates.iScience · 2025Article
- Discovery of A-967079 as an Enterovirus D68 Antiviral by Targeting the Viral 2C Protein.ACS infectious diseases · 2024Article
- Stilbenoid compounds inhibit NF-κB-mediated inflammatory responses in theFrontiers in immunology · 2023Article
- Potent Activation of Human but Not Mouse TRPA1 by JT010.International journal of molecular sciences · 2022Article
- Transient receptor potential channel involvement in antinociceptive effect of citral in orofacial acute and chronic pain models.EXCLI journal · 2022Article
- Voltage-dependent modulation of TRPA1 currents by diphenhydramine.Cell calcium · 2020Article
- Analysis of TRPA1 antagonist, A-967079, in plasma using high-performance liquid chromatography tandem mass-spectrometry.Journal of pharmaceutical analysis · 2020Article
- 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
- Article
- Identification of possible hypoxia sensor for behavioral responses in a marine annelid,Biology open · 2019Article
- TRPA1 ankyrin repeat six interacts with a small molecule inhibitor chemotype.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- PF-06526290 can both enhance and inhibit conduction through voltage-gated sodium channels.British journal of pharmacology · 2018Article
- Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition.The Journal of general physiology · 2018Article
- Identification of a putative binding site critical for general anesthetic activation of TRPA1.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Evolutionary tuning of TRPA1 and TRPV1 thermal and chemical sensitivity in vertebrates.Temperature (Austin, Tex.) · 2017Review
- Structural basis of TRPA1 inhibition by HC-030031 utilizing species-specific differences.Scientific reports · 2016Article
- Differential Activation of TRP Channels in the Adult Rat Spinal Substantia Gelatinosa by Stereoisomers of Plant-Derived Chemicals.Pharmaceuticals (Basel, Switzerland) · 2016Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transient receptor potential ankyrin 1 (TRPA1) is a Ca(2+)-permeable, nonselective cation channel mainly expressed in a subset of nociceptive neurons. TRPA1 functions as a cellular sensor detecting mechanical, chemical, and thermal stimuli. Because TRPA1 is considered to be a key player in nociception and inflammatory pain, TRPA1 antagonists have been developed as analgesic agents. Recently, by utilizing species differences, we identified the molecular basis of the antagonistic action of A967079, one of the most potent mammalian TRPA1 antagonists. Here, we show a unique effect of A967079 on TRPA1 from diverse vertebrate species, i.e. it acts as an agonist but not as an antagonist for chicken and frog TRPA1s. By characterizing chimeric channels of human and chicken TRPA1s, as well as point mutants, we found that a single specific amino acid residue located within the putative fifth transmembrane domain was involved in not only the stimulatory but also the inhibitory actions of A967079. AP18, structurally related to A967079, exerted similar pharmacological properties to A967079. Our findings and previous reports on species differences in the sensitivity to TRPA1 antagonists supply useful information in the search for novel analgesic medicines targeting TRPA1.
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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.