Affinage

TRPA1

Transient receptor potential cation channel subfamily A member 1 · UniProt O75762

Length
1119 aa
Mass
127.5 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPA1 is a polymodal non-selective cation channel that functions as a chemosensor, thermosensor, and signaling hub in nociceptive sensory neurons and diverse non-neuronal cells (PMID:15046718, PMID:17237762). Its defining activation mode is covalent modification of reactive intracellular cysteines: electrophilic compounds (mustard oil, cinnamaldehyde, ligustilide) bind cytosolic cysteines, and a single highly reactive residue, Cys621, is sufficient to open the channel, with the picomolar agonist JT010 acting site-selectively at this position (PMID:17237762, PMID:26630251, PMID:21894528). Cryo-EM resolved a two-step electrophile mechanism in which C621 modification reorients a cytoplasmic loop to promote modification of nearby C665, stabilizing an activating configuration that widens the selectivity filter and opens a cytoplasmic gate; a conserved calcium-binding pocket underlies calcium-dependent potentiation, desensitization, and activation downstream of metabotropic receptors (PMID:32641835). Beyond electrophiles, TRPA1 is gated by intracellular zinc through cysteine/histidine residues after zinc entry (PMID:19202543), by ROS generated through photosensitization (PMID:27170124), and intrinsically by both cold and heat as a bidirectional thermosensor, confirmed with purified protein (PMID:27349477); bradykinin-driven, PLC-dependent signaling provides an indirect GPCR activation route (PMID:15046718). Channel output is tuned by PKA phosphorylation of S86, S317, S428, and S972 (PMID:28076424), by Annexin A2, which limits surface availability and dampens TRPA1-dependent pain (PMID:25355205), and by assembly into TRPV1::TRPA1 heteromeric tetramers in which TRPA1 exerts a functional inhibition on TRPV1 (PMID:24643480). These properties make TRPA1 a sensor of noxious electrophiles, oxidative stress, and tissue insult that drives nocifensive behavior and neuropeptide release (PMID:27434506, PMID:28894590), and it performs distinct roles across cell types: initiating neurovascular coupling in capillary endothelium (PMID:33635784), driving GABAergic suppression of hippocampal circuits in astrocytes (PMID:36787749), mediating oxidative retinal cell death in ischemia-reperfusion (PMID:32801314), and epigenetically steering macrophage polarization via stabilization of Ezh2 (PMID:32325260). Whether TRPA1 is functionally expressed in cardiomyocytes is contested between positive (PMID:30735434) and negative (PMID:33819369) reports.

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2004 High

    Established TRPA1 as the molecular target of diverse pungent natural irritants and linked it to inflammatory GPCR signaling, framing it as a nociceptive sensor.

    Evidence Calcium imaging, electrophysiology in heterologous systems, in vivo nociception, and PLC inhibition downstream of bradykinin

    PMID:15046718

    Open questions at the time
    • Did not define the molecular site of agonist action
    • Mechanism of PLC coupling to the channel left unresolved
  2. 2004 High

    Proposed TRPA1 as a candidate hair-cell mechanotransduction channel, raising the question of whether it is intrinsically mechanosensitive.

    Evidence Immunolocalization to hair bundle tips plus morpholino knockdown in zebrafish and mouse with electrophysiology and dye uptake

    PMID:15483558

    Open questions at the time
    • Did not demonstrate direct mechanical gating of purified channel
    • Role as the definitive transduction channel later questioned by the field
  3. 2007 High

    Resolved how electrophiles activate TRPA1, showing covalent modification of reactive cytosolic cysteines rather than classical ligand binding gates the channel.

    Evidence Click chemistry, mass spectrometry identification of labeled cysteines, mutagenesis, excised-patch recording, and DTT reduction

    PMID:17237762

    Open questions at the time
    • Did not rank the relative contribution of individual cysteines
    • Structural consequence of cysteine modification unknown
  4. 2008 Medium

    Demonstrated a cysteine-independent activation route, showing TRPA1 gating is not exclusively electrophilic.

    Evidence Excised patch and whole-cell electrophysiology with a quadruple cysteine mutant and farnesyl thiosalicylic acid

    PMID:18171730

    Open questions at the time
    • Binding site for non-electrophilic activator not identified
    • Single lab, single agonist
  5. 2009 High

    Identified intracellular zinc as a TRPA1 activator acting through a permeation-then-gating mechanism, broadening the channel's chemosensory repertoire.

    Evidence Calcium imaging, patch-clamp, cysteine/histidine mutagenesis, and in vivo nociception

    PMID:19202543

    Open questions at the time
    • Physiological source of zinc activating TRPA1 in vivo unclear
  6. 2009 Medium

    Showed native TRPA1 behavior requires TRPV1, indicating channel properties depend on partner channels rather than TRPA1 alone.

    Evidence Whole-cell patch-clamp comparing trigeminal neurons to heterologous TRPA1 and TRPA1+TRPV1 systems

    PMID:19419422

    Open questions at the time
    • Did not establish physical heteromerization
    • Stoichiometry unresolved at this stage
  7. 2014 High

    Demonstrated direct TRPV1::TRPA1 heteromeric channel assembly and that TRPA1 functionally inhibits TRPV1, explaining cross-channel regulation.

    Evidence Concatemer construction, patch-clamp, AFM imaging, and antibody epitope labeling

    PMID:24643480

    Open questions at the time
    • Native abundance of heteromers in sensory neurons not quantified
    • Structural interface between subunits undefined
  8. 2014 High

    Identified Annexin A2 as a physical regulator controlling TRPA1 surface availability and pain output, defining a trafficking-level control point.

    Evidence Unbiased proteomics, Co-IP, calcium imaging, surface biotinylation, and behavior in AnxA2-deficient mice

    PMID:25355205

    Open questions at the time
    • Molecular mechanism by which AnxA2 limits membrane insertion unresolved
  9. 2016 High

    Established TRPA1 as an intrinsic bidirectional thermosensor independent of cellular context and showed redox tuning of temperature sensitivity.

    Evidence Lipid bilayer and whole-cell patch clamp, purified-protein tryptophan fluorescence, and CGRP release

    PMID:27349477

    Open questions at the time
    • Structural basis of bidirectional temperature gating not defined
  10. 2016 High

    Showed ROS/singlet oxygen from photosensitization directly activates purified TRPA1, linking oxidative chemistry to channel gating.

    Evidence Heterologous electrophysiology, sensory-neuron imaging, single-channel recording of purified hTRPA1 in bilayers, and neuropeptide release

    PMID:27170124

    Open questions at the time
    • Specific oxidized residues mediating ROS activation not mapped
  11. 2017 Medium

    Mapped PKA sensitization to four phosphorylation sites, defining a kinase-driven mechanism for TRPA1 potentiation.

    Evidence Site-directed mutagenesis, patch-clamp, and calcium imaging

    PMID:28076424

    Open questions at the time
    • Single lab, single study
    • Endogenous signaling context driving these phosphorylations not established
  12. 2018 Medium

    Revealed an extracellular activation mode in which microRNA-711 binds the S5-S6 loop to gate TRPA1 and elicit itch, expanding activator classes beyond intracellular chemistry.

    Evidence Calcium imaging, electrophysiology, molecular dynamics, extracellular-loop mutagenesis, blocking peptides, and in vivo behavior

    PMID:30033153

    Open questions at the time
    • Single lab; unconventional mechanism awaits independent confirmation
    • Endogenous sources of activating miRNA in disease unclear
  13. 2020 High

    Provided the structural framework for electrophile gating, defining a two-step cysteine mechanism coupled to selectivity-filter widening, gate opening, and a calcium-binding pocket.

    Evidence Cryo-EM combined with electrophysiology and mutagenesis

    PMID:32641835

    Open questions at the time
    • Structural basis of thermal and ROS gating not captured
    • Conformational dynamics of full gating cycle incomplete
  14. 2020 High

    Extended TRPA1 chemosensing to cannabidiol detection in vagal afferents, identifying a defined endogenous-pharmacology activation route.

    Evidence Calcium imaging, patch-clamp, and TRPA1/TRPV1 knockout mice with antagonists

    PMID:32965166

    Open questions at the time
    • Binding site for CBD on TRPA1 not identified
  15. 2023 High

    Defined cell-type-specific physiological roles of TRPA1 across endothelium, astrocytes, retina, macrophages, and cortical neurons, establishing functions beyond peripheral nociception.

    Evidence In vivo two-photon imaging, vessel myography, cell-type-specific and global knockouts, ChIP-PCR, GABA measurement, and behavioral assays

    PMID:28424320 PMID:28894590 PMID:32325260 PMID:32801314 PMID:33635784 PMID:36787749

    Open questions at the time
    • Activating stimuli for TRPA1 in each non-neuronal context not fully defined
    • Whether shared gating chemistry underlies all roles unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether TRPA1 is functionally expressed and active in cardiomyocytes remains unresolved given directly contradictory positive and negative reports.
  • Discrepancy between localization/functional claim and specific-agonist negative result unresolved
  • Cardiac expression level near detection threshold complicates interpretation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140299 molecular sensor activity 4 GO:0005198 structural molecule activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-112316 Neuronal System 2
Partners
ANXA2EZH2TRPV1
Complex memberships
TRPV1::TRPA1 heteromeric channel

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 TRPA1 is activated by pungent natural compounds (cinnamaldehyde, cinnamon oil, wintergreen oil, clove oil, mustard oil, ginger) and by the inflammatory peptide bradykinin acting through its G protein-coupled receptor. Phospholipase C (PLC) was identified as an important signaling component for TRPA1 activation downstream of bradykinin. Calcium imaging, electrophysiology in heterologous expression systems, in vivo nociceptive behavior assays, PLC inhibitor experiments Neuron High 15046718
2007 TRPA1 is activated by covalent modification of reactive cysteine residues. Click chemistry demonstrated that mustard oil and cinnamaldehyde derivatives covalently bind mouse TRPA1. Mass spectrometry identified 14 cytosolic cysteines labeled by iodoacetamide, three of which are required for normal channel function. Reactive compounds activated TRPA1 in excised patches with currents maintained after washout, and disulfide-bond-forming activation was blocked by the reducing agent DTT. Click chemistry, mass spectrometry, excised patch electrophysiology, site-directed mutagenesis, DTT reduction assay Nature High 17237762
2004 TRPA1 is expressed at the tips of hair cell bundles in the inner ear coinciding developmentally with onset of mechanosensitivity. Antibody labeling showed tip localization that disappeared upon chemical disruption of the transduction apparatus. Inhibition of TRPA1 expression in zebrafish and mouse inner ears inhibited receptor cell function as assessed by electrical recording and channel-permeant dye accumulation, identifying TRPA1 as a candidate mechanosensory transduction channel in vertebrate hair cells. Immunolocalization, antisense morpholino knockdown in zebrafish, electrophysiological recording, fluorescent dye uptake assay Nature High 15483558
2009 Zinc activates TRPA1 through a two-step mechanism: zinc first enters through TRPA1 channels and then activates TRPA1 via specific intracellular cysteine and histidine residues. Low nanomolar intracellular zinc concentrations activate TRPA1 and modulate its sensitivity. Calcium imaging, patch-clamp electrophysiology, site-directed mutagenesis of cysteine and histidine residues, in vivo nociception assays Nature Chemical Biology High 19202543
2020 Structural studies revealed a two-step electrophile activation mechanism in TRPA1: modification of a highly reactive cysteine (C621) promotes reorientation of a cytoplasmic loop to enhance nucleophilicity and modification of a nearby cysteine (C665), stabilizing the loop in an activating configuration. This modulates two permeation restrictions: widening of the selectivity filter to enhance calcium permeability and opening of a canonical gate at the cytoplasmic end of the pore. A conserved calcium-binding pocket accounts for calcium-dependent TRPA1 regulation including potentiation, desensitization, and activation by metabotropic receptors. Cryo-EM structural studies, electrophysiology, site-directed mutagenesis Nature High 32641835
2009 TRPA1-mediated responses in sensory neurons exhibit distinct characteristics (variable activation/desensitization kinetics, voltage dependency influenced by extracellular Ca2+) that cannot be replicated in cells expressing TRPA1 alone, but are restored when TRPA1 and TRPV1 are co-expressed, demonstrating functional interaction between the two channels. Whole-cell patch-clamp electrophysiology in trigeminal ganglion neurons and heterologous expression systems with TRPA1 and/or TRPV1 European Journal of Neuroscience Medium 19419422
2014 TRPV1 and TRPA1 form functional heteromeric channels. TRPV1::TRPA1 concatemers assembled as tetramers (confirmed by AFM imaging and antibody labeling showing 180° symmetry, indicating two TRPV1::TRPA1 units face-to-face). TRPV1::TRPA1 heteromers were activated by TRPV1 agonists but not TRPA1 agonists, showed only two capsaicin-binding sites, reduced total current, and TRPA1 exerted a functional inhibition on TRPV1 in the heteromeric context. Subunit concatemer construction, patch-clamp electrophysiology, atomic force microscopy (AFM) imaging, antibody epitope labeling Pflügers Archiv High 24643480
2015 Cys621 is a single, highly reactive cysteine residue in TRPA1 sufficient to open the channel upon selective covalent modification. The potent agonist JT010 (EC50 = 0.65 nM) acts by covalently and site-selectively binding Cys621. Screening of 1657 electrophilic molecules, calcium imaging, electrophysiology, site-directed mutagenesis of Cys621 Journal of the American Chemical Society High 26630251
2017 PKA sensitizes TRPA1 by phosphorylating four specific residues: S86, S317, S428, and S972, identified as the principal targets of PKA-mediated phosphorylation. Site-directed mutagenesis, patch-clamp electrophysiology, calcium imaging PLoS ONE Medium 28076424
2014 Annexin A2 (AnxA2) physically associates with native TRPA1 in mouse sensory neurons (identified by unbiased proteomics). AnxA2 limits TRPA1 membrane availability; AnxA2-deficient sensory neurons show increased TRPA1 membrane levels and higher calcium responses to TRPA1 activation. In vivo, AnxA2 deficiency results in enhanced nocifensive behaviors specifically in TRPA1-dependent pain paradigms. Unbiased proteomics, co-immunoprecipitation, calcium imaging, surface biotinylation/membrane fractionation, in vivo behavioral assays in knockout mice Journal of Neuroscience High 25355205
2016 Human TRPA1 functions as a bidirectional (U-shaped) thermosensor responding to both cold and heat. Redox modification and ligands affect both cold and heat sensing properties. Purified hTRPA1 intrinsic tryptophan fluorescence experiments in the absence of lipid bilayer confirmed intrinsic thermosensing capacity. Redox state modifies the temperature sensitivity. Lipid bilayer patch clamp, whole-cell patch clamp, purified protein tryptophan fluorescence spectroscopy, CGRP release assay from mouse trachea Scientific Reports High 27349477
2008 Farnesyl thiosalicylic acid activates TRPA1 through a mechanism distinct from reactive electrophiles. Using a TRPA1 quadruple cysteine mutant (reactive cysteines abolished), farnesyl thiosalicylic acid still activated the channel in excised patches in a calcium-independent manner, demonstrating a non-cysteine-reactive activation pathway. Whole-cell electrophysiology, excised patch recording, calcium fluorescence assay, site-directed mutagenesis Molecular Pharmacology Medium 18171730
2011 Ligustilide activates TRPA1 via cysteine-dependent (electrophilic) modification, similar to mustard oil. Mutation of reactive cysteines (C622S, C642S, C666S) dramatically reduced activation by both mustard oil and ligustilide. Its aromatization product dehydroligustilide showed inhibitory activity via a cysteine-independent mechanism. Calcium imaging, patch-clamp electrophysiology, site-directed mutagenesis of reactive cysteines Pflügers Archiv Medium 21894528
2016 Photosensitization by blue light generates reactive oxygen species (ROS/singlet oxygen) that activate TRPA1 (and to lesser extent TRPV1). Purified human TRPA1 reconstituted in artificial lipid bilayers showed single-channel activity only in the presence of protoporphyrin IX and blue light. Pretreatment with aminolevulinic acid or protoporphyrin IX dramatically increased light sensitivity of TRPA1 via ROS generation. Heterologous expression with electrophysiology, calcium imaging in sensory neurons, purified human TRPA1 in artificial lipid bilayers (single-channel recording), neuropeptide release assay from mouse tissue Journal of Neuroscience High 27170124
2016 Crotalphine selectively activates TRPA1 at picomolar concentrations requiring intact N-terminal cysteine residues, followed by strong and long-lasting homologous desensitization of the channel. Heterologous desensitization was also observed in cultured DRG neurons. TRPA1-mediated desensitization was abolished by HC030031 and absent in TRPA1-deficient mice, explaining crotalphine's analgesic action. Electrophysiology in heterologous expression and DRG neurons, CGRP release assay from trachea, in vivo behavioral assays in wild-type and TRPA1 knockout mice, pharmacological blockade Pain High 27434506
2021 TRPA1 channels in capillary endothelial cells function as neuronal activity sensors that initiate neurovascular coupling (functional hyperemia). Activation of endothelial TRPA1 in capillary beds initiates retrograde signals with biphasic propagation: slow intercellular Ca2+ signals in capillaries converted to rapid electrical signals in transitional segments that dilate upstream arterioles. TRPA1 was necessary for functional hyperemia and neurovascular coupling in the somatosensory cortex in vivo. In vivo two-photon calcium imaging, electrophysiology, pressure myography of isolated vessels, TRPA1 knockout mice, pharmacological inhibition eLife High 33635784
2023 Social deprivation upregulates TRPA1 in hippocampal astrocytes, leading to increased Ca2+ activity. Astrocyte-specific deletion of TRPA1 reversed physiological and cognitive deficits associated with social deprivation. Mechanistically, astrocytic TRPA1 increased production and release of the inhibitory neurotransmitter GABA, which suppressed hippocampal circuit function. Astrocyte-specific conditional TRPA1 knockout, Ca2+ imaging, electrophysiology, GABA measurement, behavioral testing Neuron High 36787749
2018 Extracellular miR-711 binds to and activates TRPA1 through its core sequence GGGACCC at the extracellular S5-S6 loop of TRPA1. Computer simulations and mutagenesis of critical S5-S6 loop residues confirmed this binding site. miR-711 activation of TRPA1 elicits itch and is distinct from AITC-mediated activation. Calcium imaging, electrophysiology in heterologous cells and sensory neurons, molecular dynamics simulation, mutagenesis of extracellular loop residues, in vivo behavioral assays, blocking peptide experiments Neuron Medium 30033153
2022 PKA and PKC regulate TRPA1 function and expression following paclitaxel treatment. Inhibition of PKA and PKC (but not PI3K) reduced paclitaxel-induced increases in TRPA1 mRNA, protein expression, and TRPA1-mediated Ca2+ currents in SH-SY5Y neuronal cells. qPCR, Western blot, Ca2+ imaging, patch-clamp electrophysiology, selective kinase inhibitors Neurochemical Research Medium 36098890
2014 Activation of TRPA1 and TRPV4 in human odontoblast-like cells stimulates ATP release. TRPA1 agonists (allyl isothiocyanate, cinnamaldehyde) caused concentration-dependent increases in intracellular Ca2+ and ATP release in odontoblast culture medium, both blocked by selective TRPA1 antagonists HC030031 and AP18. Ca2+ imaging with Fura-2, luciferin-luciferase ATP assay, RT-PCR, selective antagonist pharmacology Journal of Dental Research Medium 25062738
2013 TRPA1 channels in rat odontoblasts mediate mechanosensitivity (membrane stretch via hypotonic stimulation) and contribute to low-temperature sensing. Hypotonic-induced Ca2+ increase was blocked by HC030031 (TRPA1 antagonist) but not by TRPM8 antagonist, specifically implicating TRPA1 in mechanoresponsiveness. Intracellular Ca2+ imaging (Fura-2), selective pharmacological antagonists, hypo-osmotic mechanical stimulation PLoS ONE Medium 24358160
2017 TRPA1 mediates organophosphate (malathion)-induced delayed neuropathy. Malathion activates TRPA1 (but not other neuronal TRP channels), increases intracellular calcium and neuronal excitability in DRG neurons. TRPA1 knockout or pharmacological blockade (HC030031) attenuated neuropathological changes and nocifensive behaviors in mice and hens. Ca2+ imaging, patch-clamp electrophysiology, TRPA1 knockout mice, pharmacological antagonism, histopathology in mouse and hen models Cell Discovery High 28894590
2020 TRPA1 in cardiomyocytes mediated acrolein-induced Ca2+ overload and hypercontraction. TRPA1 protein was localized to intercalated disks (co-localizing with connexin43) in isolated cardiomyocytes. TRPA1 antagonist HC-030031 blocked acrolein-induced Ca2+ accumulation and hypercontraction equivalently to a Na+/Ca2+ exchange inhibitor. TRPA1 null mice showed significantly smaller myocardial infarct size after ischemia-reperfusion. Immunofluorescence colocalization, electrophysiology, Ca2+ imaging in isolated cardiomyocytes, TRPA1 knockout mice in vivo ischemia-reperfusion model, RT-PCR, Western blot American Journal of Physiology - Heart and Circulatory Physiology Medium 30735434
2021 NEGATIVE FINDING: Specific TRPA1 agonists (JT010, PF-4840154, AITC) failed to elicit TRPA1-mediated responses in native and electrically paced primary cardiomyocytes or cardiomyocyte cell lines (H9c2, HL-1), and TRPA1 mRNA was only marginal in cardiomyocytes. This argues against a direct functional role of TRPA1 in cardiomyocytes specifically. Microfluorimetry (Ca2+ imaging), RT-qPCR in primary mouse cardiomyocytes, H9c2, HL-1 cell lines, and human post-mortem heart samples; human iPSC-derived cardiomyocytes Acta Physiologica Medium 33819369
2020 Cannabidiol (CBD) activates TRPA1 in vagal afferent neurons. CBD-evoked Ca2+ influx and inward currents were prevented by TRPA1 antagonist A967079 and were absent in TRPA1 KO mice but persisted in TRPV1 KO mice. Chronic cannabis vapor exposure reduced CBD responses coinciding with loss of TRPA1 signaling. Ca2+ imaging, whole-cell patch clamp, TRPA1 and TRPV1 genetic knockout mice, pharmacological antagonism Journal of Neurophysiology High 32965166
2017 TRPA1 is functionally expressed in layer 5 pyramidal neurons of the rodent somatosensory cortex. AITC application increased intracellular Ca2+ and depolarized L5 neurons, both effects blocked by TRPA1 antagonist HC-030031 and absent in TRPA1 knockout mice. Optovin-mediated photoactivation of TRPA1 in individual L5 neurons provided optogenetic control of cortical neuronal activity. Immunostaining, whole-cell electrophysiology, two-photon Ca2+ imaging, two-photon photoswitching with optovin, TRPA1 knockout mice Open Biology Medium 28424320
2020 TRPA1 mediates oxidative stress-induced retinal cell death in ischemia-reperfusion injury. TRPA1 genetic deletion protected retinas from I/R damage, reduced infiltrating macrophages, 4-HNE (oxidative stress biomarker), and active caspase-3 levels. TRPA1 knockout in contrast to TRPV1 or TRPV4 knockout was protective, demonstrating specificity. TRPA1 also amplified the oxidative stress signal (NADPH oxidase-1 pathway implicated). TRPA1, TRPV1, TRPV4 knockout mice, in vivo retinal I/R model, histology, immunofluorescence, TRPA1 antagonist eye drops, NADPH oxidase inhibitor Cell Death & Disease High 32801314
2020 TRPA1 in macrophages interacts with Ezh2, a subunit of polycomb repressive complex 2, suppressing proteasome-dependent Ezh2 degradation. This allows TRPA1 to epigenetically regulate H3K27 trimethylation, shifting macrophage polarization away from M1 proinflammatory phenotype and attenuating atherosclerosis progression. RNA-seq, Western blot, ELISA, ChIP-PCR, luciferase reporter assay, TRPA1-/-ApoE-/- double knockout mice on high-fat diet, bone marrow-derived macrophage culture Atherosclerosis Medium 32325260

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 1471 15046718
2007 Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 921 17237762
2004 TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 522 15483558
2012 The functions of TRPA1 and TRPV1: moving away from sensory nerves. British journal of pharmacology 331 22233379
2008 Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bethesda, Md.) 331 19074743
2005 How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation. Molecular pain 204 15847696
2014 TRPA1. Handbook of experimental pharmacology 186 24756722
2020 TRPA1 as a therapeutic target for nociceptive pain. Expert opinion on therapeutic targets 179 32838583
2014 The TRPA1 channel in inflammatory and neuropathic pain and migraine. Reviews of physiology, biochemistry and pharmacology 179 24668446
2009 Zinc activates damage-sensing TRPA1 ion channels. Nature chemical biology 174 19202543
2009 TRPA1-mediated responses in trigeminal sensory neurons: interaction between TRPA1 and TRPV1. The European journal of neuroscience 164 19419422
2020 Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature 148 32641835
2006 Response of Drosophila to wasabi is mediated by painless, the fly homolog of mammalian TRPA1/ANKTM1. Current biology : CB 144 16647259
2015 TRPA1 as a drug target--promise and challenges. Naunyn-Schmiedeberg's archives of pharmacology 136 25640188
2018 TRPA1: a molecular view. Journal of neurophysiology 135 30485151
2010 Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology 134 21185837
2011 TRPA1 antagonists as potential analgesic drugs. Pharmacology & therapeutics 123 22119554
2014 The TRPA1 channel in migraine mechanism and treatment. British journal of pharmacology 118 24206166
2016 Human TRPA1 is a heat sensor displaying intrinsic U-shaped thermosensitivity. Scientific reports 116 27349477
2011 TRPV1 and TRPA1 function and modulation are target tissue dependent. The Journal of neuroscience : the official journal of the Society for Neuroscience 116 21775597
2021 Brain endothelial cell TRPA1 channels initiate neurovascular coupling. eLife 114 33635784
2021 A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment. The Journal of experimental medicine 113 33620419
2010 Irritating channels: the case of TRPA1. The Journal of physiology 109 21078588
2014 Direct evidence for functional TRPV1/TRPA1 heteromers. Pflugers Archiv : European journal of physiology 108 24643480
2012 TRPA1 channels in the vasculature. British journal of pharmacology 96 22563804
2018 TRPA1 Antagonists for Pain Relief. Pharmaceuticals (Basel, Switzerland) 93 30388732
2009 Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia. Pain 93 19464796
2018 miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus. Neuron 86 30033153
2011 Regulation of nociceptive transmission at the periphery via TRPA1-TRPV1 interactions. Current pharmaceutical biotechnology 81 20932255
2013 TRPA1: a transducer and amplifier of pain and inflammation. Basic & clinical pharmacology & toxicology 77 24102997
2015 Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity. Seminars in immunopathology 72 26403087
2014 TRPA1 and TRPV4 activation in human odontoblasts stimulates ATP release. Journal of dental research 70 25062738
2016 Photosensitization in Porphyrias and Photodynamic Therapy Involves TRPA1 and TRPV1. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 27170124
2015 Species-specific temperature sensitivity of TRPA1. Temperature (Austin, Tex.) 69 27227025
2013 TRPA1 and other TRP channels in migraine. The journal of headache and pain 69 23941062
2009 Cough: The Emerging Role of the TRPA1 Channel. Lung 65 20091046
2015 Localization and expression of TRPV1 and TRPA1 in the human oropharynx and larynx. Neurogastroenterology and motility 58 26530852
2021 TRPA1 Expression and Pathophysiology in Immune Cells. International journal of molecular sciences 57 34768891
2015 A Potent and Site-Selective Agonist of TRPA1. Journal of the American Chemical Society 55 26630251
2019 ROS/TRPA1/CGRP signaling mediates cortical spreading depression. The journal of headache and pain 54 30841847
2010 TRPA1 receptors in cough. Pulmonary pharmacology & therapeutics 51 21074632
2008 Activation of TRPA1 by farnesyl thiosalicylic acid. Molecular pharmacology 51 18171730
2011 The role of TRPA1 in visceral inflammation and pain. Channels (Austin, Tex.) 50 21993194
2021 The Role of TRPA1 in Skin Physiology and Pathology. International journal of molecular sciences 49 33802836
2021 TRPV1 and TRPA1 Channels Are Both Involved Downstream of Histamine-Induced Itch. Biomolecules 49 34439832
2017 TRPA1 expression and its functional activation in rodent cortex. Open biology 49 28424320
2013 Functional expression of TRPM8 and TRPA1 channels in rat odontoblasts. PloS one 49 24358160
2017 Molecular basis of TRPA1 regulation in nociceptive neurons. A review. Physiological research 48 28730837
2015 Involvement of TRPV1 and TRPA1 in incisional intraoral and extraoral pain. Journal of dental research 48 25576470
2022 TRPA1 Role in Inflammatory Disorders: What Is Known So Far? International journal of molecular sciences 47 35562920
2020 TRPA1 mediates damage of the retina induced by ischemia and reperfusion in mice. Cell death & disease 47 32801314
2017 Evolutionary tuning of TRPA1 and TRPV1 thermal and chemical sensitivity in vertebrates. Temperature (Austin, Tex.) 47 28680930
2011 Ligustilide: a novel TRPA1 modulator. Pflugers Archiv : European journal of physiology 47 21894528
2021 Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1. International journal of molecular sciences 46 33806052
2019 TRPA1 channel contributes to myocardial ischemia-reperfusion injury. American journal of physiology. Heart and circulatory physiology 46 30735434
2023 Social deprivation induces astrocytic TRPA1-GABA suppression of hippocampal circuits. Neuron 44 36787749
2023 Inflammation-the role of TRPA1 channel. Frontiers in physiology 44 36875034
2020 TRPA1 regulates macrophages phenotype plasticity and atherosclerosis progression. Atherosclerosis 44 32325260
2019 Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod-induced, psoriasiform dermal inflammation in mice. Journal of cellular and molecular medicine 44 31111624
2019 The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges. Frontiers in pharmacology 44 31680989
2017 Sensitization of TRPA1 by Protein Kinase A. PloS one 44 28076424
2021 The irritant receptor TRPA1 mediates the mosquito repellent effect of catnip. Current biology : CB 43 33667373
2016 TRPA1 gene polymorphisms and childhood asthma. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 43 27779810
2015 Interaction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves. Pulmonary pharmacology & therapeutics 43 26283426
2007 TRPA1. Handbook of experimental pharmacology 43 17217068
2019 Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling. International journal of molecular sciences 42 30974795
2015 Transient receptor potential ankyrin 1 (TRPA1) antagonists. Pharmaceutical patent analyst 42 25853468
2019 A Human TRPA1-Specific Pain Model. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 30862667
2016 Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? Pharmaceuticals (Basel, Switzerland) 40 27827953
2020 Transient receptor potential ankyrin 1 (TRPA1) antagonists: a patent review (2015-2019). Expert opinion on therapeutic patents 37 32686526
2014 TRPA1 channels: chemical and temperature sensitivity. Current topics in membranes 36 25366234
2017 Recent Progress in the Discovery and Development of TRPA1 Modulators. Progress in medicinal chemistry 34 28314413
2016 Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia. Pain 34 27434506
2022 The role of TRPA1 channels in thermosensation. Cell insight 33 37193355
2019 Validation of antibodies for the specific detection of human TRPA1. Scientific reports 32 31811235
2016 Acute cardiopulmonary toxicity of inhaled aldehydes: role of TRPA1. Annals of the New York Academy of Sciences 32 27152448
2014 Annexin A2 regulates TRPA1-dependent nociception. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 25355205
2017 TRPA1 channel mediates organophosphate-induced delayed neuropathy. Cell discovery 31 28894590
2023 Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells. Cells 30 37174661
2016 Transient Receptor Potential Ankyrin 1 (TRPA1) Channel and Neurogenic Inflammation in Pathogenesis of Asthma. Medical science monitor : international medical journal of experimental and clinical research 30 27539812
2017 Methylglyoxal Requires AC1 and TRPA1 to Produce Pain and Spinal Neuron Activation. Frontiers in neuroscience 29 29270106
2023 Research Progress on TRPA1 in Diseases. The Journal of membrane biology 28 37039840
2018 TRPM8 and TRPA1 do not contribute to dental pulp sensitivity to cold. Scientific reports 28 30181551
2023 Transient receptor potential ankyrin 1 (TRPA1) modulators: Recent update and future perspective. European journal of medicinal chemistry 27 37269667
2015 How the TRPA1 receptor transmits painful stimuli: Inner workings revealed by electron cryomicroscopy. BioEssays : news and reviews in molecular, cellular and developmental biology 27 26387779
2009 TRPA1 modulators in preclinical development. Expert opinion on therapeutic patents 26 19939193
2021 Inhibition of TRPA1 reduces airway inflammation and hyperresponsiveness in mice with allergic rhinitis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 33774861
2016 Cannabinoid receptors and TRPA1 on neuroprotection in a model of retinal ischemia. Experimental eye research 24 27876485
2017 Chemical and thermal sensitivity of medaka TRPA1 analyzed in heterologous expression system. Biochemical and biophysical research communications 23 29037810
2021 No functional TRPA1 in cardiomyocytes. Acta physiologica (Oxford, England) 22 33819369
2022 Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC. Neurochemical research 21 36098890
2022 Modulation of Glia Activation by TRPA1 Antagonism in Preclinical Models of Migraine. International journal of molecular sciences 20 36430567
2021 The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma. Cells 20 34831352
2018 Atypical pharmacology of schistosome TRPA1-like ion channels. PLoS neglected tropical diseases 20 29746471
2023 Diisocyanates influence models of atopic dermatitis through direct activation of TRPA1. PloS one 19 36877675
2023 TRPA1 rare variants in chronic neuropathic and nociplastic pain patients. Pain 19 37079850
2021 Role of TRPA1 in Tissue Damage and Kidney Disease. International journal of molecular sciences 19 33810314
2021 TRPA1: Pharmacology, natural activators and role in obesity prevention. European journal of pharmacology 19 34627805
2020 Cannabidiol activation of vagal afferent neurons requires TRPA1. Journal of neurophysiology 19 32965166
2016 TRPA1 receptor is upregulated in human oral lichen planus. Oral diseases 19 27718297

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