ArticleThe Journal of biological chemistry2008
TRPA1 mediates the noxious effects of natural sesquiterpene deterrents.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 101 citations in OpenAlex.
- Anti-Inflammatory and Analgesic Properties ofBiomedicines · 2026Review
- Sesquiterpene Lactone Derivatives ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Agonism of mosquito and human transient receptor potential ankyrin 1 (TRPA1) channels by the natural drimane sesquiterpene cinnamodial.bioRxiv : the preprint server for biology · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway.Molecules (Basel, Switzerland) · 2025Article
- Inhaled Volatile Molecules-Responsive TRP Channels as Non-Olfactory Receptors.Biomolecules & therapeutics · 2024Review
- Pharmacologic Inhibition of Transient Receptor Potential Ion Channel Ankyrin 1 Counteracts 2-Chlorobenzalmalononitrile Tear Gas Agent-Induced Cutaneous Injuries.The Journal of pharmacology and experimental therapeutics · 2024Article
- The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia.Frontiers in aging neuroscience · 2023Review
- Anticancer Activity of Natural and Semi-Synthetic Drimane and Coloratane Sesquiterpenoids.Molecules (Basel, Switzerland) · 2022Review
- Biosynthesis of Fungal Drimane-Type Sesquiterpene Esters.Angewandte Chemie (International ed. in English) · 2021Article
- Halogen-Induced Chemical Injury to the Mammalian Cardiopulmonary Systems.Physiology (Bethesda, Md.) · 2021Review
- The Role of TRPA1 in Skin Physiology and Pathology.International journal of molecular sciences · 2021Review
- Transient receptor potential channels in pulmonary chemical injuries and as countermeasure targets.Annals of the New York Academy of Sciences · 2020Article
- TRPA1 as a therapeutic target for nociceptive pain.Expert opinion on therapeutic targets · 2020Review
- Electrophile-Induced Conformational Switch of the Human TRPA1 Ion Channel Detected by Mass Spectrometry.International journal of molecular sciences · 2020Article
- Semi-synthetic cinnamodial analogues: Structural insights into the insecticidal and antifeedant activities of drimane sesquiterpenes against the mosquito Aedes aegypti.PLoS neglected tropical diseases · 2020Article
- Article
- Formation of flavorant-propylene Glycol Adducts With Novel Toxicological Properties in Chemically Unstable E-Cigarette Liquids.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Article
- Activation Stoichiometry and Pore Architecture of TRPA1 Probed with Channel Concatemers.Scientific reports · 2018Article
- Regulation of Pain and Itch by TRP Channels.Neuroscience bulletin · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Plants, fungi, and animals generate a diverse array of deterrent natural products that induce avoidance behavior in biological adversaries. The largest known chemical family of deterrents are terpenes characterized by reactive alpha,beta-unsaturated dialdehyde moieties, including the drimane sesquiterpenes and other terpene species. Deterrent sesquiterpenes are potent activators of mammalian peripheral chemosensory neurons, causing pain and neurogenic inflammation. Despite their wide-spread synthesis and medicinal use as desensitizing analgesics, their molecular targets remain unknown. Here we show that isovelleral, a noxious fungal sesquiterpene, excites sensory neurons through activation of TPRA1, an ion channel involved in inflammatory pain signaling. TRPA1 is also activated by polygodial, a drimane sesquiterpene synthesized by plants and animals. TRPA1-deficient mice show greatly reduced nocifensive behavior in response to isovelleral, indicating that TRPA1 is the major receptor for deterrent sesquiterpenes in vivo. Isovelleral and polygodial represent the first fungal and animal small molecule agonists of nociceptive transient receptor potential channels.
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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.