Nomenclature: TRPA1

Family: Transient Receptor Potential channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 0 1119 8q13 TRPA1 transient receptor potential cation channel, subfamily A, member 1 59
Mouse 6 0 1125 1 A3 Trpa1 transient receptor potential cation channel, subfamily A, member 1 119
Rat 6 0 1125 5q11 Trpa1 transient receptor potential cation channel, subfamily A, member 1 60
Previous and Unofficial Names
P120
TRPN1
ANKTM1
ankyrin-like with transmembrane domains 1
ankyrin-like with transmembrane domains protein 1
transient receptor potential cation channel subfamily A member 1
transient receptor potential cation channel, subfamily A, member 1
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Functional Characteristics
γ = 87–100 pS; conducts mono- and di-valent cations non-selectively (PCa/PNa = 0.84); outward rectification; activated by elevated intracellular Ca2+
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  Ca2+ = Na+ > Mg2+
References:  90
Ion Selectivity and Conductance Comments
TRPA1 exhibits conductance of 98pS in physiological solution, dependent on Ca2+ and Mg2+ concentration [90].
Voltage Dependence Comments
Voltage-dependence not yet described, inactivation by extracellular Ca2+ might be voltage dependent [90].
Other chemical activators (Human)
Isothiocyanates (covalent) and 1,4-dihydropyridines (non-covalent)
Physical activators (Human)
Cooling (<17°C) (disputed)
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
methyl salicylate Mm Agonist - - 6x10-4 Physiological 8
Conc range: 6x10-4 M [8]
Holding voltage: Physiological
eugenol Mm Agonist - - 6x10-4 Physiological 8
Conc range: 6x10-4 M [8]
Holding voltage: Physiological
gingerol Mm Agonist - - 6x10-4 Physiological 8
Conc range: 6x10-4 M [8]
Holding voltage: Physiological
icilin Mm Agonist - - 1x10-4 Physiological 119
Conc range: 1x10-4 M non-covalent [119]
Holding voltage: Physiological
(-)-menthol Hs Activation - - 1x10-6 - 1x10-4 -
Conc range: 1x10-6 - 1x10-4 M non-covalent
PF-4840154 Hs Activation 7.6 pEC50 - - 111
pEC50 7.6 This compound has similar activity at rat and mouse TRPA1 [111]
Description: Calcium imaging
Conditions: HEK-293cells expressing TRPA1
dibenzoxazepine Hs Activation 7.2 pEC50 - - 24
pEC50 7.2 [24]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4.
morphanthridine Hs Activation 7.1 pEC50 - - 24
pEC50 7.1 [24]
Description: Patch clamp
Conditions: HEK293 cells expressing human TRPA1
1'-acetoxychavicol acetate Hs Activation 6.8 pEC50 - - 92
pEC50 6.8 [92]
Description: FlexStation 2 Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4
chlorobenzylidene malononitrile Hs Activation 6.7 pEC50 - - 24
pEC50 6.7 (EC50 1.99x10-7 M) covalent [24]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4.
chloropicrin Hs Activation 6.7 pEC50 - - 17
pEC50 6.7 This compound also activates mouse TRPA1 [17]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2
omega-chloroacetophenone Hs Activation 6.6 pEC50 - - 24
pEC50 6.6 [24]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4.
NPPB Hs Activation 6.49 pEC50 - - 76
pEC50 6.49 [76]
Description: FLIPR calcium influx assay
Conditions: HEK293 cells expressing human TRPA1 loaded with Calcium-4 dye
benzoquinone Hs Activation 6.4 pEC50 - - 2
pEC50 6.4 [2]
Description: Calcium imaging
Conditions: CHO cells expressing TRPA1 loaded with Fura-2
isovelleral Hs Activation 6.3 pEC50 - - 42
pEC50 6.3 This compound is also an activator of mouse TRPA1. [42]
Description: Calcium imaging
Conditions: HEK293 cells expressing human or mouse TRPA1
Cu2+ Mm Activation 6.22 pEC50 - - 4,87
pEC50 6.22 (EC50 6x10-7 M) [4,87]
super cinnamaldehyde Mm Activation 6.1 pEC50 - - 78
pEC50 6.1 (EC50 8x10-7 M) [78]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: CHO cells expressing mouse TRPA1
auranofin Hs Activation 6.0 pEC50 - - 54
pEC50 6.0 [54]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fura-2
bromoacetone Hs Activation 6.0 pEC50 - - 17
pEC50 6.0 This compound also activates mouse TRPA1 [17]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2dorsal root ganglion neurons
allicin Mm Agonist 5.9 pEC50 - Physiological 79
pEC50 5.9 [79]
Holding voltage: Physiological
Cu2+ Hs Activation 5.89 pEC50 - - 4,87
pEC50 5.89 (EC50 1.3x10-6 M) [4,87]
Description: Sodium imaging
Conditions: CHO cells expressing human TRPA1
Cd2+ Hs Activation 5.85 pEC50 - - 4,87
pEC50 5.85 (EC50 1.4x10-6 M) [4,87]
Description: Sodium and calcium imaging
Conditions: CHO cells expressing human TRPA1 and mouse dorsal root ganglion neurons
artepillin C Hs Activation 5.74 pEC50 - - 52
pEC50 5.74 (EC50 1.8x10-6 M) [52]
Description: Calcium imaging
Conditions: HEK293 cells transfected with human TRPA1 loaded with Fura-2
4-oxo-nonenal Mm Activation 5.7 pEC50 - - 3
pEC50 5.7 [3]
Description: Calcium imaging
Conditions: CHO cells expressing mouse TRPA1 loaded with Fura-2
nitrooleic acid Hs Activation 5.7 pEC50 - - 124
pEC50 5.7 This compound has a similar activity at mouse TRPA1 [124]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse trigeminal and vagal neurons loaded with Fura-2
Cd2+ Mm Activation 5.68 pEC50 - - 4,87
pEC50 5.68 (EC50 2.1x10-6 M) [4,87]
N-acetyl-4-benzoquinoneimine Rn Activation 5.6 pEC50 - - 2,95
pEC50 5.6 This compound has similar activity at human and mouse TRPA1 [2,95]
Description: Calcium imaging
Conditions: CHO or HEK293 cells expressing rat/mouse/human TRPA1 loaded with Fura-2
oleocanthal Hs Activation 5.6 pEC50 - -60.0 106
pEC50 5.6 [106]
Holding voltage: -60.0 mV
Description: Patch clamp
Conditions: HEK-293 cells expressing human TRPA1
1,6-hexamethylene diisocyanate Hs Activation 5.6 pEC50 - - 17
pEC50 5.6 This compound also activates mouse TRPA1 [17]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2
O3 Hs Activation 5.5 pEC50 - - 125
pEC50 5.5 Ozone has similar activity at mouse TRPA1 [125]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse vagal neurons loaded with Fura-2
acrolein Hs Agonist 5.3 pEC50 - Physiological 12
pEC50 5.3 (EC50 5.011x10-6 M) covalent [12]
Holding voltage: Physiological
farnesylthiosalicylic acid Hs Activation 5.3 pEC50 - - 82
pEC50 5.3 [82]
Description: FLIPR calcium-influx assay
Conditions: CHO-TREx cells loaded with Fluo-3
allicin Hs Agonist 5.1 pEC50 - Physiological 13
pEC50 5.1 (EC50 7.943x10-6 M) covalent [13]
Holding voltage: Physiological
apomorphine Hs Activation 5.1 pEC50 - - 113
pEC50 5.1 Apomorphine blocks TRPA1 at 100µM [113]
Description: Calcium imaging, patch clamp
Conditions: HEK293 cells transfected with human TRPA1
allyl isothiocyanate Rn Activation 5.0 pEC50 - -40.0 60
pEC50 5.0 [60]
Holding voltage: -40.0 mV
benzyl bromide Hs Activation 4.9 pEC50 - - 17
pEC50 4.9 This compound also activates mouse TRPA1 [17]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2
Δ9-tetrahydrocannabinol Hs Agonist 4.9 pEC50 - -60.0 60
pEC50 4.9 (EC50 1.259x10-5 M) non-covalent [60]
Holding voltage: -60.0 mV
nicotine Hs Activation 4.8 pEC50 - -75.0 123
pEC50 4.8 (EC50 1.7x10-5 M) non-covalent [123]
Holding voltage: -75.0 mV
Description: Patch clamp
Conditions: CHO cells expressing mouse or human TRPA1
thymol Hs Activation 4.7 pEC50 6.25x10-6 - 2.5x10-5 - 74
pEC50 4.7 (EC50 2x10-5 M) Conc range: 6.25x10-6 - 2.5x10-5 M non-covalent [74]
Description: FLIPR calcium influx assay
Conditions: Human TRPA1-HEK293 stable cell line loaded with calcium 3 dye
allyl isothiocyanate Mm Activation 4.7 pEC50 - Physiological 8
pEC50 4.7 [8]
Holding voltage: Physiological
methyl isocyanate Hs Activation 4.6 pEC50 - - 17
pEC50 4.6 This compound also activates mouse TRPA1 [17]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2
crotylaldehyde Rn Activation 4.6 pEC50 - - 6
pEC50 4.6 [6]
Description: Calcium imaging
Conditions: HEK293 cells expressing rat TRPA1 loaded with Fura-2
prostaglandin A2 Mm Activation 4.6 pEC50 - - 83
pEC50 4.6 [83]
Description: Calcium imaging
Conditions: Mouse dorsal root ganglion neurons loaded with Fura-2
URB597 Hs Agonist 4.6 pEC50 - - 100
pEC50 4.6 (EC50 2.4x10-5 M) non-covalent [100]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: HEK293 cells expressing human TRPA1
dibutyl phthalate Hs Activation 4.6 pEC50 - - 115
pEC50 4.6 [115]
Description: Calcium imaging
Conditions: CHO cells stably expressing human TRPA1 loaded with Fluo-4
4-hydroxynonenal Rn Activation 4.6 pEC50 - - 81,128
pEC50 4.6 [81,128]
Description: Calcium imaging
Conditions: Rat dorsal root ganglion neurons
(-)-menthol Hs Partial agonist 4.5 pEC50 - - 61,138
pEC50 4.5 Menthol is also active at the mouse TRPA1, but becomes inhibitory at >100µM [61,138]
Description: Calcium imaging, patch clamp
Conditions: CHO cells expressing human TRPA1
docosahexaenoic acid Rn Activation 4.4 pEC50 - -60.0 88
pEC50 4.4 This compound has similar activity at human and mouse TRPA1 [88]
Holding voltage: -60.0 mV
Description: Patch clamp
Conditions: HEK293 celss expressing rat TRPA1
methylglyoxal Hs Activation 2.5 – 6.0 pEC50 - - 27,37,67
pEC50 2.5 – 6.0 This compound has similar activity at mouse and rat TRPA1 [27,37,67]
Description: Calcium imaging, patch clamp
Conditions: HEK 293 cells expressing hTRPA1, rTRPA1 loaded with Fura-2
cinnamaldehyde Mm Agonist 4.2 pEC50 - Physiological 8
pEC50 4.2 (EC50 6.3x10-5 M) covalent [8]
Holding voltage: Physiological
acetaldehyde Hs Activation 4.1 pEC50 - - 9
pEC50 4.1 [9]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-3
flufenamic acid Rn Activation 3.8 pEC50 - -100.0 58
pEC50 3.8 [58]
Holding voltage: -100.0 mV
Description: Two electrode voltage clamp
Conditions: Xenopus oocytes expressing rat TRPA1
isoflurane Rn Activation 3.7 pEC50 - - 84
pEC50 3.7 [84]
Description: Patch clamp
Conditions: HEK293 cells expressing rat TRPA1
H2O2 Mm Activation 3.6 pEC50 - - 3,112
pEC50 3.6 [3,112]
Description: Calcium imaging
Conditions: CHO cells expressing mouse TRPA1 loaded with Fura-2
2-iodoacetamide Mm Activation 3.45 pEC50 - - 78
pEC50 3.45 (EC50 3.57x10-4 M) [78]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: CHO cells expressing mouse TRPA1
formalin Mm Activation 3.4 pEC50 - - 81,85
pEC50 3.4 (EC50 3.981x10-4 M) covalent. This level of activity is also observed for rat TRPA1 [81,85]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4
niflumic acid Rn Activation 3.3 pEC50 - -100.0 58
pEC50 3.3 [58]
Holding voltage: -100.0 mV
Description: Two electrode voltage clamp
Conditions: Xenopus oocytes expressing rat TRPA1
NaHS Mm Activation 2.9 pEC50 - - 120
pEC50 2.9 This compound has similar activity at the human TRPA1 [120]
Description: Calcium imaging
Conditions: HEK293 cells expressing mouse TRPA1 loaded with Fura-2
acetaldehyde Mm Activation 2.9 pEC50 - - 9
pEC50 2.9 [9]
Description: Calcium imaging
Conditions: HEK293 cells expressing mouse TRPA1loaded with Fluo-3
MTSEA Mm Activation 2.8 pEC50 - - 78
pEC50 2.8 (EC50 1.58x10-3 M) [78]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: CHO cells expressing mouse TRPA1
methyl p-hydroxybenzoate Mm Activation 2.4 pEC50 - -60.0 46
pEC50 2.4 [46]
Holding voltage: -60.0 mV
Description: Patch clamp
Conditions: HEK293 cells expressing mouse TRPA1
Zn2+ Mm Activation 2.3 pEC50 - - 4,57
pEC50 2.3 Zinc has similar activity at the human TRPA1 [4,57]
Description: Calcim imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglia neurons loaded with Fura-2
NH4Cl Mm Activation 2.0 pEC50 - - 47
pEC50 2.0 [47]
Description: Patch clamp
Conditions: HEK293 cells expressing mouse TRPA1
View species-specific activator tables
Activator Comments
TRPA1 is activated by covalent modification of intracellular cysteines [55], activated by bradykinin [8,12,60], probably activated by noxious cold [8,119], but this is disputed [60,90], mechano-activation is still under discussion. TRPA1 is modulated by intra- and extracellular Ca2+ [90].

Snake and fly TRPA1 are a heat-activated channels [48,99,132].

In a calcium imaging study the PGD2 metabolite 15-deoxy-Δ12,14-prostaglandin J2 activated the human TRPA1 expressed in HEK293 cells and in a subset of chemosensitive mouse trigeminal neurons, where this activation was blocked by both the nonselective TRP channel blocker ruthenium red, and the TRPA1 inhibitor HC-030031. Δ12-PGJ2 and 8-iso-PGA2 are also activators of TRPA1 [126].

Further compounds which are reported to activate TRPA1 in vitro include: 2-pentenal (mouse) [12], clotrimazole (human and mouse) [86], WIN55,212-2 (mouse) [1] and AM1241 (mouse) [1], sodium hypochlorite (NaOCl; mouse and human) [18], 5,6-EET (mouse) [116], hepoxilin A3 (mouse, rat) [50], 12(S)-HpETE (mouse, rat) [50], carbon dioxide (rat, mouse) [134], acetic, propinoic, formic, and lactic acids (human, rat, mouse) [133].
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
resolvin D2 Mm Inhibition 8.7 pIC50 - -60.0 103
pIC50 8.7 [103]
Holding voltage: -60.0 mV
Description: Patch-clamp
Conditions: Mouse DRG neurons, mustard oil AITC (300 µM)
resolvin D1 Mm Inhibition 7.2 pIC50 - - 10,103
pIC50 7.2 [10,103]
Description: Calcium imaging, patch clamp
Conditions: Mouse DRG neurons, mustard oil AITC (300 µM); HEK293T cells transfected with mTRPs
A-967079 Hs Inhibition 7.2 pIC50 - - 30
pIC50 7.2 This compoud also acts as a gating inhibitor at the rat and mouse TRPA1. [30]
Description: Calcium imaging
Conditions: HEK-293F cells expressing TRPA1
AP18 Hs Inhibition 5.51 pIC50 - - 105
pIC50 5.51 (IC50 3.1x10-6 M) [105]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: CHO cells expressing human TRPA1
AP18 Mm Inhibition 5.35 pIC50 - - 105
pIC50 5.35 (IC50 4.5x10-6 M) [105]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
HC030031 Hs Inhibition 5.2 pIC50 - - 85
pIC50 5.2 [85]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4
gentamicin Mm Antagonist 5.2 pIC50 - -80.0 90
pIC50 5.2 [90]
Holding voltage: -80.0 mV
isopentenyl diphosphate Mm Inhibition 5.1 pIC50 - - 10
pIC50 5.1 [10]
Description: Calcium imaging
Conditions: HEK-293 cells expressing TRPA1
chembridge-5861528 Hs Inhibition 4.8 pIC50 - - 135
pIC50 4.8 [135]
Description: Calcium imaging
Conditions: Human TRPA1-inducible HEK-293 cells (HEK-LacltrpA1 clone B22), Aallyl isothiocyanate as agonist
(-)-menthol Mm Antagonist 4.2 pIC50 - Physiological 80
pIC50 4.2 [80]
Holding voltage: Physiological
camphor Mm Antagonist 4.2 pIC50 - Physiological 80
pIC50 4.2 [80]
Holding voltage: Physiological
View species-specific gating inhibitor tables
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Gd3+ Mm Antagonist 7.0 pIC50 - -80.0 90
pIC50 7.0 [90]
Holding voltage: -80.0 mV
ruthenium red Mm - 5.5 pIC50 - -80.0 90
pIC50 5.5 [90]
Holding voltage: -80.0 mV
amiloride Mm Inhibition 3.3 pIC50 - -80.0 90
pIC50 3.3 [90]
Holding voltage: -80.0 mV
Channel Blocker Comments
Blocking effects are modulated by divalent cations [90].
Tissue Distribution
Respiratory system: including lung fibroblasts, airway epithelial and smooth muscle cells
Species:  Human
Technique:  RT-PCR, western blot, immunocytochemistry
References:  89,97
Brain, heart, small intestine, lung, skeletal muscle, and pancreas.
Species:  Human
Technique:  Northern Blot
References:  118
Skin cells (including fibroblasts, keratinocytes and melanocytes).
Species:  Human
Technique:  RT-PCR, Western blot, calcium imaging
References:  15,25,129
Gastrointestinal tissues (including stomach, intestine, epithelial cell, duodenal mucosa), enterochromaffin cells. NOTE: this pattern of expression is also reported in mouse.
Species:  Human
Technique:  RT-PCR, in situ hybridization, flow cytometoric analysis
References:  68,101,107,109
Urinary bladder (basal layers of the urothelium, urothelial cells and nerve fibres within the urothelium, suburothelial space, and muscle layer and around blood vessels). Note that this pattern of expression is also observed in the rat.
Species:  Human
Technique:  Immunohistochemistry, Western blot and RT-PCR.
References:  49,120
Odontoblast and dental pulp fibroblasts.
Species:  Human
Technique:  RT-PCR, immunohistochemistry, calcium imaging and Western blot.
References:  39-40
Synoviocyte
Species:  Human
Technique:  RT-PCR
References:  53
Dorsal root ganglia, sensory neurones (C-fibres), trigeminal ganglia, nodose ganglia, nociceptive neurones, inner ear (organ of Corti).
Species:  Mouse
Technique:  In situ hybridisation, northern blot, RT-PCR, immunohistochemistry
References:  13,31,60,66,90,119
Olfactory epithelium
Species:  Mouse
Technique:  Immunohistochemistry
References:  91
Jugular/nodose ganglion neurons
Species:  Mouse
Technique:  RT-PCR
References:  93
Nerve fibers innervating the vestibular sensory cells.
Species:  Mouse
Technique:  Immunohistochemistry
References:  122
Endothelial cells from cerebral arteries.
Species:  Rat
Technique:  RT-PCR
References:  36
Pancreatic beta cells.
Species:  Rat
Technique:  RT-PCR, immunocytochemistry, western blotting
References:  27
Tissue Distribution Comments
Note that expression is upregulated by de-ubiquitination by the tumor suppressor (ubiquitin hydrolase) CYLD.
Functional Assays
Two-electrode voltage clamp, patch clamp, single channel analysis and Ca2+ imaging (reported in mouse, rat and human).
Species:  Mouse
Tissue:  Xenopus laevis oocytes injected with TRPA1 cDNA, transfection of HEK, CHO cells.
Response measured:  Activation by ligands and cold
References:  31,60,90,119
Physiological Functions
Senses various noxious stimuli: pungent natural compounds, noxious cold temperature, environmental irritants, inflammatory peptides, noxious mechanical stimuli.
Species:  Mouse
Tissue:  Sensory neurones.
References:  104
Bladder overaction (due to spinal cord injury and bladder hyperreflexia, afferent transduction).
Species:  Rat
Tissue:  Bladder and dorsal root ganglion neurons.
References:  5,35
Mediates vasodilation and regulates blood flow. Note that this has also been reported in rat.
Species:  Mouse
Tissue:  Cardiovascular system including skin, blood vessels (ear, paw), mesenteric, carotid, cerebral and meningeal artery.
References:  36,71,96,108
Insulin release
Species:  Rat
Tissue:  Pancreatic beta cells
References:  27
Cough; observed in human, guinea pig and mouse.
Species:  Human
Tissue:  Vagus nerve
References:  7,20
Facilitating excitatory synaptic transmission.
Species:  Rat
Tissue:  Substantia gelatinosa neurons
References:  69
Colitis
Species:  Mouse
Tissue:  Colon
References:  41
Sense hyperoxia and hypoxia
Species:  Mouse
Tissue:  Nodose ganglion and dorsal root ganglia neurons.
References:  121
Regulation of gastrointestinal motility. Note that this has also been described in guinea pig.
Species:  Mouse
Tissue:  Ileum, colon and myenteric neurons.
References:  101,107
Itch
Species:  Mouse
Tissue:  Dorsal root ganglia neurons, skin
References:  44,75,77,136-137
Visceral nociception
Species:  Mouse
Tissue:  Dorsal root ganglia neurons innervating the colon.
References:  28
Pancreatic inflammation and pain
Species:  Mouse
Tissue:  Pancreatic nerve fibers and dorsal root ganglia neurons innervating the pancreas.
References:  29,114
Allergic asthma and non-allergic airway hyperreactivity. Observed in mouse and rat.
Species:  Mouse
Tissue:  Airway
References:  26,56,110
Melanin synthesis
Species:  Human
Tissue:  Skin
References:  15
Inflammatory and neuropathic pain (reported in rat and mouse)
Species:  Rat
Tissue: 
References:  21,32-33,38,98,102,127
Allergic contact dermatitis
Species:  Mouse
Tissue:  Dorsal root ganglion neurons
References:  75,115
Mechanosensation and mechanical transduction.
Species:  Mouse
Tissue:  Sensory neurons, skin, colon and nerve.
References:  22-23,73,131
Nociception and mediator of pro-algesic effects of bradykinin, receptor for noxious cold (disputed).
Species:  Mouse
Tissue:  Sensory neurons (nodose and dorsal root ganglion).
References:  12,33-34,43,62,72,119
Physiological Consequences of Altering Gene Expression
Antisense knock down of TRPA1 alleviates cold hyperalgesia after spinal nerve ligation.
Species:  Rat
Tissue:  Spinal cord
Technique:  Antisense oligodeoxynucleotide gene knockdown.
References:  64
Reduced TRPA1 expression leads to normalized bladder spontaneous phasic activity, decreases the cinnamaldehyde-induced bladder contraction and the number of nonvoiding contractions in spinal cord injuried rat.
Species:  Rat
Tissue:  Spinal cord.
Technique:  Antisense oligodeoxynucleotide gene knockdown.
References:  5
Mice lacking TRPA1 gene show impaired detection of pungent natural compounds, noxious cold temperature, environmental irritants, inflammatory peptides, noxious mechanical stimuli (reported in human, mouse and rat).
Species:  Mouse
Tissue:  Dorsal root ganglion neurons
Technique:  Gene knockout
References:  104
Mice lacking TRPA1 gene show reduced inflammatory responses to certain chronic diseases, including chronic skin diseases, asthma, rheumatoid arthritis, colitis, etc. (reported in human, mouse and rat).
Species:  Mouse
Tissue:  Skin, colon, lung, dorsal root ganglion neurons
Technique: 
References:  14,16
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpa1+|Trpa1tm1Jul Trpa1tm1Jul/Trpa1+
involves: 129P2/OlaHsd * C57BL/6
MGI:3522699  MP:0002498 abnormal acute inflammation PMID: 16564016 
Trpa1tm1.1Bju Trpa1tm1.1Bju/Trpa1tm1.1Bju
involves: C57BL/6J
MGI:3522699  MP:0002330 abnormal bronchial provocation PMID: 19059884 
Trpa1+|Trpa1tm1Jul Trpa1tm1Jul/Trpa1+
involves: 129P2/OlaHsd * C57BL/6
MGI:3522699  MP:0002734 abnormal mechanical nociception PMID: 16564016 
Trpa1tm1Jul Trpa1tm1Jul/Trpa1tm1Jul
involves: 129P2/OlaHsd * C57BL/6
MGI:3522699  MP:0003633 abnormal nervous system physiology PMID: 16564016 
Trpa1+|Trpa1tm1Jul Trpa1tm1Jul/Trpa1+
involves: 129P2/OlaHsd * C57BL/6
MGI:3522699  MP:0003633 abnormal nervous system physiology PMID: 16564016 
Trpa1tm1.1Bju Trpa1tm1.1Bju/Trpa1tm1.1Bju
involves: C57BL/6J
MGI:3522699  MP:0004811 abnormal neuron physiology PMID: 18499726  19059884 
Trpa1tm1.1Bju Trpa1tm1.1Bju/Trpa1tm1.1Bju
involves: C57BL/6J
MGI:3522699  MP:0010055 abnormal sensory neuron physiology PMID: 18499726 
Trpa1tm1Kykw Trpa1tm1Kykw/Trpa1tm1Kykw
involves: 129P2/OlaHsd * C57BL/6J
MGI:3522699  MP:0001986 abnormal taste sensitivity PMID: 16630838 
Trpa1+|Trpa1tm1Jul Trpa1tm1Jul/Trpa1+
involves: 129P2/OlaHsd * C57BL/6
MGI:3522699  MP:0002733 abnormal thermal nociception PMID: 16564016 
Trpa1tm1Kykw Trpa1tm1Kykw/Trpa1tm1Kykw
involves: 129P2/OlaHsd * C57BL/6J
MGI:3522699  MP:0003663 abnormal thermosensation PMID: 16630838 
Trpa1tm1.1Bju Trpa1tm1.1Bju/Trpa1tm1.1Bju
involves: C57BL/6J
MGI:3522699  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 19059884 
Trpa1+|Trpa1tm1Jul Trpa1tm1Jul/Trpa1+
involves: 129P2/OlaHsd * C57BL/6
MGI:3522699  MP:0005407 hyperalgesia PMID: 16564016 
Trpa1tm1Kykw Trpa1tm1Kykw/Trpa1tm1Kykw
involves: 129P2/OlaHsd * C57BL/6J
MGI:3522699  MP:0005498 hyporesponsive to tactile stimuli PMID: 16630838 
Trpa1tm1Kykw Trpa1tm1Kykw/Trpa1tm1Kykw
involves: 129P2/OlaHsd * C57BL/6J
MGI:3522699  MP:0004764 increased brainstem auditory evoked potential PMID: 16630838 
Trpa1+|Trpa1tm1Jul Trpa1tm1Jul/Trpa1+
involves: 129P2/OlaHsd * C57BL/6
MGI:3522699  MP:0008531 increased chemical nociceptive threshold PMID: 16564016 
Trpa1tm1Kykw Trpa1tm1Kykw/Trpa1tm1Kykw
involves: 129P2/OlaHsd * C57BL/6J
MGI:3522699  MP:0001973 increased thermal nociceptive threshold PMID: 16630838 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Familial Episodic Pain Syndrome (FEPS)
OMIM:  615040
References:  70
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human N855S An autosomal-dominant familial episodic pain syndrome characterized by episodes of debilitating upper body pain, triggered by fasting and physical stress. A point mutation (N855S) in S4 transmembrane segment of TRPA1. 70
Gene Expression and Pathophysiology
Upregulation
Tissue or cell type:  Dorsal root ganglia
Pathophysiology:  Diabetes
Species:  Rat
Technique: 
References:  11
Upregulation
Tissue or cell type:  Bladder and dorsal root ganglia neurons.
Pathophysiology:  Spinal cord injury
Species:  Rat
Technique: 
References:  5
Overexpression, upregulation of the channel in sensory neurones following injury and inflammation contributes to cold hyperalgesia.
Tissue or cell type:  Nociceptory neurones.
Pathophysiology:  Hyperalgesia
Species:  Rat
Technique: 
References:  102
Upregulation
Tissue or cell type:  Synoviocytes
Pathophysiology:  Inflammation
Species:  Human
Technique: 
References:  53
Upregulation
Tissue or cell type:  Dorsal root ganglia
Pathophysiology:  Oxaliplatin-induced peripheral neuropathy
Species:  Mouse
Technique: 
References:  94
Downregulation
Tissue or cell type:  Dorsal root ganglion neurons.
Pathophysiology:  Neuropathic pain (spared nerve injury).
Species:  Rat
Technique: 
References:  117
Upregulation
Tissue or cell type:  Spinal cord and dorsal root ganglia.
Pathophysiology:  CFA induced inflammatory pain.
Species:  Mouse
Technique: 
References:  32,63
Upreguation. Note that this is also observed in rat.
Tissue or cell type:  Colon, dorsal root ganglia.
Pathophysiology:  Colitis.
Species:  Mouse
Technique: 
References:  65,139
Upreguation
Tissue or cell type:  Lumbar dorsal root ganglia.
Pathophysiology:  Chronic constriction injury (CCI) of the sciatic nerve.
Species:  Rat
Technique: 
References:  45
Upregulation
Tissue or cell type:  Dorsal root ganglia and nodose ganglion neurons innervating the pancreas.
Pathophysiology:  Pancreatic pain
Species:  Mouse
Technique: 
References:  114
Upregulation
Tissue or cell type:  Dorsal root ganglia
Pathophysiology:  Spinal nerve ligation
Species:  Rat
Technique: 
References:  64
Upregulation
Tissue or cell type:  Trigeminal ganglia
Pathophysiology:  Tooth injury, pulp exposure
Species:  Rat
Technique: 
References:  51
Biologically Significant Variant Comments
A single nucleotide polymorphism (SNP), which results in the Glu179Lys substitution, has been found in pain patients who experience paradoxical heat sensation [19]. TRPA1 SNPs are associated with preference for mentholated cigarettes in heavy smokers [130].
General Comments
Note that Drs Liu and Fan contributed equally to the September 2013 update of this page.

REFERENCES

1. Akopian AN, Ruparel NB, Patwardhan A, Hargreaves KM. (2008) Cannabinoids desensitize capsaicin and mustard oil responses in sensory neurons via TRPA1 activation. J. Neurosci.28 (5): 1064-75. [PMID:18234885]

2. Andersson DA, Gentry C, Alenmyr L, Killander D, Lewis SE, Andersson A, Bucher B, Galzi JL, Sterner O, Bevan S et al.. (2011) TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ(9)-tetrahydrocannabiorcol. Nat Commun2: 551. [PMID:22109525]

3. Andersson DA, Gentry C, Moss S, Bevan S. (2008) Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J. Neurosci.28 (10): 2485-94. [PMID:18322093]

4. Andersson DA, Gentry C, Moss S, Bevan S. (2009) Clioquinol and pyrithione activate TRPA1 by increasing intracellular Zn2+. Proc. Natl. Acad. Sci. U.S.A.106 (20): 8374-9. [PMID:19416844]

5. Andrade EL, Forner S, Bento AF, Leite DF, Dias MA, Leal PC, Koepp J, Calixto JB. (2011) TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury. Am. J. Physiol. Renal Physiol.300 (5): F1223-34. [PMID:21367919]

6. Andrè E, Campi B, Materazzi S, Trevisani M, Amadesi S, Massi D, Creminon C, Vaksman N, Nassini R, Civelli M et al.. (2008) Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J. Clin. Invest.118 (7): 2574-82. [PMID:18568077]

7. Andrè E, Gatti R, Trevisani M, Preti D, Baraldi PG, Patacchini R, Geppetti P. (2009) Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents. Br. J. Pharmacol.158 (6): 1621-8. [PMID:19845671]

8. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A. (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron41 (6): 849-57. [PMID:15046718]

9. Bang S, Kim KY, Yoo S, Kim YG, Hwang SW. (2007) Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur. J. Neurosci.26 (9): 2516-23. [PMID:17970723]

10. Bang S, Yoo S, Yang TJ, Cho H, Kim YG, Hwang SW. (2010) Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br. J. Pharmacol.161 (3): 707-20. [PMID:20880407]

11. Barrière DA, Rieusset J, Chanteranne D, Busserolles J, Chauvin MA, Chapuis L, Salles J, Dubray C, Morio B. (2012) Paclitaxel therapy potentiates cold hyperalgesia in streptozotocin-induced diabetic rats through enhanced mitochondrial reactive oxygen species production and TRPA1 sensitization. Pain153 (3): 553-61. [PMID:22177224]

12. Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D. (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell124 (6): 1269-82. [PMID:16564016]

13. Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Högestätt ED, Julius D, Jordt SE, Zygmunt PM. (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc. Natl. Acad. Sci. U.S.A.102 (34): 12248-52. [PMID:16103371]

14. Bautista DM, Pellegrino M, Tsunozaki M. (2013) TRPA1: A gatekeeper for inflammation. Annu. Rev. Physiol.75: 181-200. [PMID:23020579]

15. Bellono NW, Kammel LG, Zimmerman AL, Oancea E. (2013) UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes. Proc. Natl. Acad. Sci. U.S.A.110 (6): 2383-8. [PMID:23345429]

16. Bessac BF, Jordt SE. (2010) Sensory detection and responses to toxic gases: mechanisms, health effects, and countermeasures. Proc Am Thorac Soc7 (4): 269-77. [PMID:20601631]

17. Bessac BF, Sivula M, von Hehn CA, Caceres AI, Escalera J, Jordt SE. (2009) Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J.23 (4): 1102-14. [PMID:19036859]

18. Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE. (2008) TRPA1 is a major oxidant sensor in murine airway sensory neurons. J. Clin. Invest.118 (5): 1899-910. [PMID:18398506]

19. Binder A, May D, Baron R, Maier C, Tölle TR, Treede RD, Berthele A, Faltraco F, Flor H, Gierthmühlen J et al.. (2011) Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients. PLoS ONE6 (3): e17387. [PMID:21468319]

20. Birrell MA, Belvisi MG, Grace M, Sadofsky L, Faruqi S, Hele DJ, Maher SA, Freund-Michel V, Morice AH. (2009) TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am. J. Respir. Crit. Care Med.180 (11): 1042-7. [PMID:19729665]

21. Bonet IJ, Fischer L, Parada CA, Tambeli CH. (2013) The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia. Neuropharmacology65: 206-12. [PMID:23098993]

22. Brierley SM, Castro J, Harrington AM, Hughes PA, Page AJ, Rychkov GY, Blackshaw LA. (2011) TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J. Physiol. (Lond.)589 (Pt 14): 3575-93. [PMID:21558163]

23. Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O'Donnell TA, Cooper NJ, Harrington AM, Adam B, Liebregts T et al.. (2009) The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli. Gastroenterology137 (6): 2084-2095.e3. [PMID:19632231]

24. Brône B, Peeters PJ, Marrannes R, Mercken M, Nuydens R, Meert T, Gijsen HJ. (2008) Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor. Toxicol. Appl. Pharmacol.231 (2): 150-6. [PMID:18501939]

25. Bíró T, Kovács L. (2009) An "ice-cold" TR(i)P to skin biology: the role of TRPA1 in human epidermal keratinocytes. J. Invest. Dermatol.129 (9): 2096-9. [PMID:19809424]

26. Caceres AI, Brackmann M, Elia MD, Bessac BF, del Camino D, D'Amours M, Witek JS, Fanger CM, Chong JA, Hayward NJ et al.. (2009) A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc. Natl. Acad. Sci. U.S.A.106 (22): 9099-104. [PMID:19458046]

27. Cao DS, Zhong L, Hsieh TH, Abooj M, Bishnoi M, Hughes L, Premkumar LS. (2012) Expression of transient receptor potential ankyrin 1 (TRPA1) and its role in insulin release from rat pancreatic beta cells. PLoS ONE7 (5): e38005. [PMID:22701540]

28. Cattaruzza F, Spreadbury I, Miranda-Morales M, Grady EF, Vanner S, Bunnett NW. (2010) Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice. Am. J. Physiol. Gastrointest. Liver Physiol.298 (1): G81-91. [PMID:19875705]

29. Ceppa E, Cattaruzza F, Lyo V, Amadesi S, Pelayo JC, Poole DP, Vaksman N, Liedtke W, Cohen DM, Grady EF et al.. (2010) Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice. Am. J. Physiol. Gastrointest. Liver Physiol.299 (3): G556-71. [PMID:20539005]

30. Chen J, Joshi SK, DiDomenico S, Perner RJ, Mikusa JP, Gauvin DM, Segreti JA, Han P, Zhang XF, Niforatos W et al.. (2011) Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain152 (5): 1165-72. [PMID:21402443]

31. Corey DP, Garcia-Anoveros J, Holt JR, Kwan KY, Lin SY, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, Geleoc GS, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D, Zhang DS. (2004) TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature432 (7018): 723-30. [PMID:15483558]

32. da Costa DS, Meotti FC, Andrade EL, Leal PC, Motta EM, Calixto JB. (2010) The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation. Pain148 (3): 431-7. [PMID:20056530]

33. del Camino D, Murphy S, Heiry M, Barrett LB, Earley TJ, Cook CA, Petrus MJ, Zhao M, D'Amours M, Deering N et al.. (2010) TRPA1 contributes to cold hypersensitivity. J. Neurosci.30 (45): 15165-74. [PMID:21068322]

34. Dhaka A, Viswanath V, Patapoutian A. (2006) Trp ion channels and temperature sensation. Annu. Rev. Neurosci.29: 135-61. [PMID:16776582]

35. Du S, Araki I, Yoshiyama M, Nomura T, Takeda M. (2007) Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway. Urology70 (4): 826-31. [PMID:17991581]

36. Earley S, Gonzales AL, Crnich R. (2009) Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ channels. Circ. Res.104 (8): 987-94. [PMID:19299646]

37. Eberhardt MJ, Filipovic MR, Leffler A, de la Roche J, Kistner K, Fischer MJ, Fleming T, Zimmermann K, Ivanovic-Burmazovic I, Nawroth PP et al.. (2012) Methylglyoxal activates nociceptors through transient receptor potential channel A1 (TRPA1): a possible mechanism of metabolic neuropathies. J. Biol. Chem.287 (34): 28291-306. [PMID:22740698]

38. Eid SR, Crown ED, Moore EL, Liang HA, Choong KC, Dima S, Henze DA, Kane SA, Urban MO. (2008) HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity. Mol Pain4: 48. [PMID:18954467]

39. El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, Killough SA, Lundy FT. (2011) Human dental pulp fibroblasts express the "cold-sensing" transient receptor potential channels TRPA1 and TRPM8. J Endod37 (4): 473-8. [PMID:21419293]

40. El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, Lundy FT. (2011) Human odontoblasts express functional thermo-sensitive TRP channels: implications for dentin sensitivity. Pain152 (10): 2211-23. [PMID:21168271]

41. Engel MA, Leffler A, Niedermirtl F, Babes A, Zimmermann K, Filipović MR, Izydorczyk I, Eberhardt M, Kichko TI, Mueller-Tribbensee SM et al.. (2011) TRPA1 and substance P mediate colitis in mice. Gastroenterology141 (4): 1346-58. [PMID:21763243]

42. Escalera J, von Hehn CA, Bessac BF, Sivula M, Jordt SE. (2008) TRPA1 mediates the noxious effects of natural sesquiterpene deterrents. J. Biol. Chem.283 (35): 24136-44. [PMID:18550530]

43. Fajardo O, Meseguer V, Belmonte C, Viana F. (2008) TRPA1 channels mediate cold temperature sensing in mammalian vagal sensory neurons: pharmacological and genetic evidence. J. Neurosci.28 (31): 7863-75. [PMID:18667618]

44. Fernandes ES, Vong CT, Quek S, Cheong J, Awal S, Gentry C, Aubdool AA, Liang L, Bodkin JV, Bevan S et al.. (2013) Superoxide generation and leukocyte accumulation: key elements in the mediation of leukotriene B₄-induced itch by transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1. FASEB J.27 (4): 1664-73. [PMID:23271050]

45. Frederick J, Buck ME, Matson DJ, Cortright DN. (2007) Increased TRPA1, TRPM8, and TRPV2 expression in dorsal root ganglia by nerve injury. Biochem. Biophys. Res. Commun.358 (4): 1058-64. [PMID:17517374]

46. Fujita F, Moriyama T, Higashi T, Shima A, Tominaga M. (2007) Methyl p-hydroxybenzoate causes pain sensation through activation of TRPA1 channels. Br. J. Pharmacol.151 (1): 153-60. [PMID:17351650]

47. Fujita F, Uchida K, Moriyama T, Shima A, Shibasaki K, Inada H, Sokabe T, Tominaga M. (2008) Intracellular alkalization causes pain sensation through activation of TRPA1 in mice. J. Clin. Invest.118 (12): 4049-57. [PMID:19033673]

48. Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, Chesler AT, Sánchez EE, Perez JC, Weissman JS, Julius D. (2010) Molecular basis of infrared detection by snakes. Nature464 (7291): 1006-11. [PMID:20228791]

49. Gratzke C, Streng T, Waldkirch E, Sigl K, Stief C, Andersson KE, Hedlund P. (2009) Transient receptor potential A1 (TRPA1) activity in the human urethra--evidence for a functional role for TRPA1 in the outflow region. Eur. Urol.55 (3): 696-704. [PMID:18468780]

50. Gregus AM, Doolen S, Dumlao DS, Buczynski MW, Takasusuki T, Fitzsimmons BL, Hua XY, Taylor BK, Dennis EA, Yaksh TL. (2012) Spinal 12-lipoxygenase-derived hepoxilin A3 contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors. Proc. Natl. Acad. Sci. U.S.A.109 (17): 6721-6. [PMID:22493235]

51. Haas ET, Rowland K, Gautam M. (2011) Tooth injury increases expression of the cold sensitive TRP channel TRPA1 in trigeminal neurons. Arch. Oral Biol.56 (12): 1604-9. [PMID:21783172]

52. Hata T, Tazawa S, Ohta S, Rhyu MR, Misaka T, Ichihara K. (2012) Artepillin C, a major ingredient of Brazilian propolis, induces a pungent taste by activating TRPA1 channels. PLoS ONE7 (11): e48072. [PMID:23133611]

53. Hatano N, Itoh Y, Suzuki H, Muraki Y, Hayashi H, Onozaki K, Wood IC, Beech DJ, Muraki K. (2012) Hypoxia-inducible factor-1α (HIF1α) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release. J. Biol. Chem.287 (38): 31962-72. [PMID:22843691]

54. Hatano N, Suzuki H, Muraki Y, Muraki K. (2013) Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin. Am. J. Physiol., Cell Physiol.304 (4): C354-61. [PMID:23220116]

55. Hinman A, Chuang HH, Bautista DM, Julius D. (2006) TRP channel activation by reversible covalent modification. Proc. Natl. Acad. Sci. U.S.A.103 (51): 19564-8. [PMID:17164327]

56. Hox V, Vanoirbeek JA, Alpizar YA, Voedisch S, Callebaut I, Bobic S, Sharify A, De Vooght V, Van Gerven L, Devos F et al.. (2013) Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice. Am. J. Respir. Crit. Care Med.187 (5): 486-93. [PMID:23262517]

57. Hu H, Bandell M, Petrus MJ, Zhu MX, Patapoutian A. (2009) Zinc activates damage-sensing TRPA1 ion channels. Nat. Chem. Biol.5 (3): 183-90. [PMID:19202543]

58. Hu H, Tian J, Zhu Y, Wang C, Xiao R, Herz JM, Wood JD, Zhu MX. (2010) Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs. Pflugers Arch.459 (4): 579-92. [PMID:19888597]

59. Jaquemar D, Schenker T, Trueb B. (1999) An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts. J. Biol. Chem.274 (11): 7325-33. [PMID:10066796]

60. Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Högestätt ED, Meng ID, Julius D. (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature427 (6971): 260-5. [PMID:14712238]

61. Karashima Y, Damann N, Prenen J, Talavera K, Segal A, Voets T, Nilius B. (2007) Bimodal action of menthol on the transient receptor potential channel TRPA1. J. Neurosci.27 (37): 9874-84. [PMID:17855602]

62. Karashima Y, Talavera K, Everaerts W, Janssens A, Kwan KY, Vennekens R, Nilius B, Voets T. (2009) TRPA1 acts as a cold sensor in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A.106 (4): 1273-8. [PMID:19144922]

63. Katsura H, Obata K, Mizushima T, Sakurai J, Kobayashi K, Yamanaka H, Dai Y, Fukuoka T, Sakagami M, Noguchi K. (2007) Activation of extracellular signal-regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation. J. Neurochem.102 (5): 1614-24. [PMID:17573825]

64. Katsura H, Obata K, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Sakagami M, Noguchi K. (2006) Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp. Neurol.200 (1): 112-23. [PMID:16546170]

65. Kimball ES, Prouty SP, Pavlick KP, Wallace NH, Schneider CR, Hornby PJ. (2007) Stimulation of neuronal receptors, neuropeptides and cytokines during experimental oil of mustard colitis. Neurogastroenterol. Motil.19 (5): 390-400. [PMID:17509021]

66. Kobayashi K, Fukuoka T, Obata K, Yamanaka H, Dai Y, Tokunaga A, Noguchi K. (2005) Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors. J. Comp. Neurol.493 (4): 596-606. [PMID:16304633]

67. Koivisto A, Hukkanen M, Saarnilehto M, Chapman H, Kuokkanen K, Wei H, Viisanen H, Akerman KE, Lindstedt K, Pertovaara A. (2012) Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in diabetic animals: sustained activation of the TRPA1 channel contributes to the pathogenesis of peripheral diabetic neuropathy. Pharmacol. Res.65 (1): 149-58. [PMID:22133672]

68. Kono T, Kaneko A, Omiya Y, Ohbuchi K, Ohno N, Yamamoto M. (2013) Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine. Am. J. Physiol. Gastrointest. Liver Physiol.304 (4): G428-36. [PMID:23275609]

69. Kosugi M, Nakatsuka T, Fujita T, Kuroda Y, Kumamoto E. (2007) Activation of TRPA1 channel facilitates excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord. J. Neurosci.27 (16): 4443-51. [PMID:17442829]

70. Kremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F, Marsh S, Woods CG, Jones NG, Paterson KJ, Fricker FR et al.. (2010) A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron66 (5): 671-80. [PMID:20547126]

71. Kunkler PE, Ballard CJ, Oxford GS, Hurley JH. (2011) TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. Pain152 (1): 38-44. [PMID:21075522]

72. Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, Corey DP. (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron50 (2): 277-89. [PMID:16630838]

73. Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL. (2009) TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J. Neurosci.29 (15): 4808-19. [PMID:19369549]

74. Lee SP, Buber MT, Yang Q, Cerne R, Cortés RY, Sprous DG, Bryant RW. (2008) Thymol and related alkyl phenols activate the hTRPA1 channel. Br. J. Pharmacol.153 (8): 1739-49. [PMID:18334983]

75. Liu B, Escalera J, Balakrishna S, Fan L, Caceres AI, Robinson E, Sui A, McKay MC, McAlexander MA, Herrick CA et al.. (2013) TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. FASEB J.,  [Epub ahead of print]. [PMID:23722916]

76. Liu K, Samuel M, Ho M, Harrison RK, Paslay JW. (2010) NPPB structure-specifically activates TRPA1 channels. Biochem. Pharmacol.80 (1): 113-21. [PMID:20226176]

77. Liu T, Ji RR. (2012) Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice. Neurosci Bull28 (2): 145-54. [PMID:22466125]

78. Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A. (2007) Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature445 (7127): 541-5. [PMID:17237762]

79. Macpherson LJ, Geierstanger BH, Viswanath V, Bandell M, Eid SR, Hwang S, Patapoutian A. (2005) The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr. Biol.15 (10): 929-34. [PMID:15916949]

80. Macpherson LJ, Hwang SW, Miyamoto T, Dubin AE, Patapoutian A, Story GM. (2006) More than cool: promiscuous relationships of menthol and other sensory compounds. Mol. Cell. Neurosci.32 (4): 335-43. [PMID:16829128]

81. Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang S, Cravatt B, Corey DP, Patapoutian A. (2007) An ion channel essential for sensing chemical damage. J. Neurosci.27 (42): 11412-5. [PMID:17942735]

82. Maher M, Ao H, Banke T, Nasser N, Wu NT, Breitenbucher JG, Chaplan SR, Wickenden AD. (2008) Activation of TRPA1 by farnesyl thiosalicylic acid. Mol. Pharmacol.73 (4): 1225-34. [PMID:18171730]

83. Materazzi S, Nassini R, Andrè E, Campi B, Amadesi S, Trevisani M, Bunnett NW, Patacchini R, Geppetti P. (2008) Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc. Natl. Acad. Sci. U.S.A.105 (33): 12045-50. [PMID:18687886]

84. Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP. (2008) General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc. Natl. Acad. Sci. U.S.A.105 (25): 8784-9. [PMID:18574153]

85. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM et al.. (2007) TRPA1 mediates formalin-induced pain. Proc. Natl. Acad. Sci. U.S.A.104 (33): 13525-30. [PMID:17686976]

86. Meseguer V, Karashima Y, Talavera K, D'Hoedt D, Donovan-Rodríguez T, Viana F, Nilius B, Voets T. (2008) Transient receptor potential channels in sensory neurons are targets of the antimycotic agent clotrimazole. J. Neurosci.28 (3): 576-86. [PMID:18199759]

87. Miura S, Takahashi K, Imagawa T, Uchida K, Saito S, Tominaga M, Ohta T. (2013) Involvement of TRPA1 activation in acute pain induced by cadmium in mice. Mol Pain9: 7. [PMID:23448290]

88. Motter AL, Ahern GP. (2012) TRPA1 is a polyunsaturated fatty acid sensor in mammals. PLoS ONE7 (6): e38439. [PMID:22723860]