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Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease
Open accessAbstract
The transient receptor potential ankyrin (TRPA) channels are Ca 2+ -permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the NH 2 terminus of the channel, an unusual structural feature that may be relevant to its interactions with intracellular components. TRPA1 is primarily involved in the detection of an extremely wide variety of exogenous stimuli that may produce cellular damage. This includes a plethora of electrophilic compounds that interact with nucleophilic amino acid residues in the channel and many other chemically unrelated compounds whose only common feature seems to be their ability to partition in the plasma membrane. TRPA1 has been reported to be activated by cold, heat, and mechanical stimuli, and its function is modulated by multiple factors, including Ca 2+ , trace metals, pH, and reactive oxygen, nitrogen, and carbonyl species. TRPA1 is involved in acute and chronic pain as well as inflammation, plays key roles in the pathophysiology of nearly all organ systems, and is an attractive target for the treatment of related diseases. Here we review the current knowledge about the mammalian TRPA1 channel, linking its unique structure, widely tuned sensory properties, and complex regulation to its roles in multiple pathophysiological conditions.
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Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation
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TRPA1 and other TRP channels in migraine
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The Role of Endothelial Ca2+ Signaling in Neurovascular Coupling: A View from the Lumen
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TRP Channels Coordinate Ion Signalling in Astroglia
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Respiratory virus infection up-regulates TRPV1, TRPA1 and ASICS3 receptors on airway cells
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Self-citationThe interphase of the formalin test
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Modulation of Transient Receptor Vanilloid 1 Activity by Transient Receptor Potential Ankyrin 1
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TRPA1 Mediates the Noxious Effects of Natural Sesquiterpene Deterrents
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Transient Receptor Potential Ankyrin 1 Mediates Toluene Diisocyanate–Evoked Respiratory Irritation
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Inhibition of transient receptor potential A1 channel by phosphatidylinositol-4,5-bisphosphate
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Functional TRP and ASIC-like channels in cultured urothelial cells from the rat
Kullmann, F. A., Shah, M. A., Birder, L. A., & de Groat, W. C. (2009) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90718.2008 · Cited by 98
Ca2+-activated K+ Channels in Murine Endothelial Cells: Block by Intracellular Calcium and Magnesium
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A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain
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Species-specific temperature sensitivity of TRPA1
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Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice
Ceppa, E. P., Cattaruzza, F., Lyo, V., Amadesi, S., Pelayo, J. C., Poole, D. P., Vaksman, N., Liedtke, W., Cohen, D., Grady, E. F., et al. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00433.2009 · Cited by 97
Activation of TRPA1 by Membrane Permeable Local Anesthetics
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The molecular and cellular basis of thermosensation in mammals
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What is the hair cell transduction channel?
Corey, D. P. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.116582 · Cited by 96
TRP channels in neurogastroenterology: opportunities for therapeutic intervention
Boesmans, W., Owsianik, G., Tack, J. F., Voets, T., & Berghe, P. V. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01009.x · Cited by 95
Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia
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Contractile effect of TRPA1 receptor agonists in the isolated mouse intestine
Penuelas, A., Tashima, K., Tsuchiya, S., Matsumoto, K., Nakamura, T., Horie, S., & Yano, S. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.08.015 · Cited by 95
TRPA1 Is Differentially Modulated by the Amphipathic Molecules Trinitrophenol and Chlorpromazine
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Regulation of Nociceptive Transmission at the Periphery Via TRPA1-TRPV1 Interactions
Akopian, A. N. (2010) · Current Pharmaceutical Biotechnology · doi:10.2174/138920111793937952 · Cited by 94
Neuroprotective effects of TRPA1 channels in the cerebral endothelium following ischemic stroke
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Balemans, D., Boeckxstaens, G. E., Talavera, K., & Wouters, M. M. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00401.2016 · Cited by 92
Self-citationDifferential effects of lipopolysaccharide on mouse sensory TRP channels
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Self-citationCough: The Emerging Role of the TRPA1 Channel
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Transient Receptor Potential Ankyrin 1 Is Expressed by Inhibitory Motoneurons of the Mouse Intestine
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Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity
Derbenev, A. V., & Zsombok, A. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0529-x · Cited by 89
TRP channel functions in the gastrointestinal tract
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Shapiro, D., Deering‐Rice, C. E., Romero, E. G., Hughen, R. W., Light, A. R., Veranth, J. M., & Reilly, C. A. (2013) · Chemical Research in Toxicology · doi:10.1021/tx400024h · Cited by 89
Zinc ions as effectors of environmental oxidative lung injury
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Diallyl sulfides in garlic activate both TRPA1 and TRPV1
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Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle
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Borkum, J. M. (2017) · Headache The Journal of Head and Face Pain · doi:10.1111/head.13214 · Cited by 86
Okubo, K., Matsumura, M., Kawaishi, Y., Aoki, Y., Matsunami, M., Okawa, Y., Sekiguchi, F., & Kawabata, A. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01886.x · Cited by 85
Nociceptive and reflexive responses recorded from the human nasal mucosa
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The TRPA 1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives
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Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine
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Transient Receptor Potential A1 Channels
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TRP channels as therapeutic targets in airway disorders: a patent review
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TRPA1 mediates bladder hyperalgesia in a mouse model of cystitis
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Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain
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Cavanaugh, E. J., Simkin, D., & Kim, D. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.048 · Cited by 82
TRP channels: new targets for visceral pain
Blackshaw, L. A., Brierley, S. M., & Hughes, P. A. (2009) · Gut · doi:10.1136/gut.2009.179523 · Cited by 82
Storozhuk, M., & Zholos, A. V. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170424120802 · Cited by 82
TRPs as Chemosensors (ROS, RNS, RCS, Gasotransmitters)
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Identification of a splice variant of mouse TRPA1 that regulates TRPA1 activity
Zhou, Y., Suzuki, Y., Uchida, K., & Tominaga, M. (2013) · Nature Communications · doi:10.1038/ncomms3399 · Cited by 81
Burning Cold: Involvement of TRPA1 in Noxious Cold Sensation
Kwan, K. Y., & Corey, D. P. (2009) · The Journal of General Physiology · doi:10.1085/jgp.200810146 · Cited by 81
TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury
de Andrade, E. L., Forner, S., Bento, A. F., Leite, D. F. P., Dias, M. A., Leal, P. C., Koepp, J., & Calixto, J. Β. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00535.2010 · Cited by 81
Andrei, S. R., Sinharoy, P., Bratz, I. N., & Damron, D. S. (2016) · Channels · doi:10.1080/19336950.2016.1185579 · Cited by 81
Photosensitization in Porphyrias and Photodynamic Therapy Involves TRPA1 and TRPV1
Babeș, A., Sauer, S. K., Moparthi, L., Kichko, T. I., Neacsu, C., Namer, B., Filipović, M. R., Zygmunt, P. M., Reeh, P. W., & Fischer, M. J. M. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4268-15.2016 · Cited by 80
Morera, E., PETROCELLIS, L. D., Morera, L., Moriello, A. S., Nalli, M., Marzo, V. D., & Ortar, G. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.12.113 · Cited by 79
Benemei, S., Logu, F. D., Puma, S. L., Marone, I. M., Coppi, E., Ugolini, F., Liedtke, W., Pollastro, F., Appendino, G., Geppetti, P., et al. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13917 · Cited by 79
Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice
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Identification of in Vivo Disulfide Conformation of TRPA1 Ion Channel
Wang, L., Cvetkov, T. L., Chance, M. R., & Moiseenkova‐Bell, V. Y. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.329748 · Cited by 78
The Emerging Role of TRP Channels in Mechanisms of Temperature and Pain Sensation
Story, G. M. (2006) · Current Neuropharmacology · doi:10.2174/157015906778019482 · Cited by 78
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Self-citationThe cell biology of acute itch
Green, D. P., & Dong, X. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201603042 · Cited by 78
TRP Channels as Sensors of Bacterial Endotoxins
Boonen, B., Alpizar, Y. A., Meseguer, V., & Talavera, K. (2018) · Toxins · doi:10.3390/toxins10080326 · Cited by 78
Self-citationFacilitation of MrgprD by TRP‐A1 promotes neuropathic pain
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The role of TRPA1 in visceral inflammation and pain
Lapointe, T. K., & Altier, C. (2011) · Channels · doi:10.4161/chan.5.6.18016 · Cited by 77
Hata, T., Tazawa, S., Ohta, S., Rhyu, M., Misaka, T., & Ichihara, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048072 · Cited by 77
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TAMURA, Y., Iwasaki, Y., Narukawa, M., & Watanabe, T. (2012) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.58.9 · Cited by 76
TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus
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Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity
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TRPA1 channels: Novel targets of 1,4-dihydropyridines
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Modulation of Oral Heat and Cold Pain by Irritant Chemicals
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A TRPA1 antagonist reverts oxaliplatin-induced neuropathic pain
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TRP Channels as Sensors of Chemically-Induced Changes in Cell Membrane Mechanical Properties
Startek, J. B., Boonen, B., Talavera, K., & Meseguer, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020371 · Cited by 75
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Bianchi, B. R., Zhang, X., Reilly, R. M., Kym, P. R., Yao, B. B., & Chen, J. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.189902 · Cited by 74
Genetically Encoded Calcium Indicators and Astrocyte Calcium Microdomains
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Zinc Inhibits TRPV1 to Alleviate Chemotherapy-Induced Neuropathic Pain
Luo, J., Bavencoffe, A. G., Yang, P., Feng, J., Yin, S., Qian, A., Yu, W., Liu, S., Gong, X., Cai, T., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1816-17.2017 · Cited by 74
The role of thymic stromal lymphopoietin in the immunopathogenesis of atopic dermatitis
Jariwala, S. P., Abrams, E. M., Benson, A. E., Fodeman, J., & Zheng, T. (2011) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2011.03797.x · Cited by 73
Yu, S., Gao, G., Peterson, B. Z., & Ouyang, A. (2009) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00068.2009 · Cited by 73
TNF-α–Induced p38MAPK Activation Regulates TRPA1 and TRPV4 Activity in Odontoblast-Like Cells
Karim, I. A. E., McCrudden, M., Linden, G. J., Abdullah, H., Curtis, T. M., McGahon, M. K., About, I., Irwin, C., & Lundy, F. T. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.07.020 · Cited by 72
Bioactive Prenylogous Cannabinoid from Fiber Hemp (Cannabis sativa)
Pollastro, F., Taglialatela‐Scafati, O., Allarà, M., Muñóz, E., Marzo, V. D., PETROCELLIS, L. D., & Appendino, G. (2011) · Journal of Natural Products · doi:10.1021/np200500p · Cited by 72
QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells
Doihara, H., Nozawa, K., Kojima, R., Kawabata-Shoda, E., Yokoyama, T., & Ito, H. (2009) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0165-7 · Cited by 72
Mukhopadhyay, I., Kulkarni, A., Aranake, S., Karnik, P., Shetty, M., Thorat, S., Ghosh, I., Wale, D. P., Bhosale, V. M., & Khairatkar-Joshi, N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097005 · Cited by 72
Cited by
Zhang, M., Ma, Y., Ye, X., Zhang, N., Pan, L., & Wang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01464-x · Cited by 522
TRPA1 rare variants in chronic neuropathic and nociplastic pain patients
Marchi, M., Salvi, E., Andelic, M., Mehmeti, E., D'Amato, I., Cazzato, D., Chiappori, F., Lombardi, R., Cartelli, D., Devigili, G., et al. (2023) · Pain · doi:10.1097/j.pain.0000000000002905 · Cited by 29
TRPA1 promotes melanosome phagocytosis in keratinocytes via PAR-2/CYLD axis
Wang, Y., Li, Z., Wu, W., Liu, Y., Xiao, Y., Qi, D., Zhao, G., Zhou, M., Wang, H., Liu, J., et al. (2022) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2022.05.005 · Cited by 12
Giacco, V., Flower, G., Artamonova, M., Hunter, J., Padilla Requerey, A., & Hamilton, N. B. (2023) · Glia · doi:10.1002/glia.24347 · Cited by 11
Metadata
- Authors
- Talavera, K., Startek, J. B., Alvarez-Collazo, J., Boonen, B., Alpizar, Y. A., Sanchez, A., Naert, R., & Nilius, B.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2020-04-01
- Volume
- 100
- Issue
- 2
- Pages
- 725-803
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2987691534
- Cited by
- 403
- References
- 728
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
