TRPA1 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

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TRPA1

target has curated data in GtoImmuPdb

Target id: 485

Nomenclature: TRPA1

Family: Transient Receptor Potential channels

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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 60
Mouse 6 0 1125 1 A3 Trpa1 transient receptor potential cation channel, subfamily A, member 1 127
Rat 6 0 1125 5q11 Trpa1 transient receptor potential cation channel, subfamily A, member 1 61
Previous and Unofficial Names
ANKTM1 | TRPN1 | ankyrin-like with transmembrane domains 1 | transient receptor potential cation channel
Database Links
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
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:  95
Ion Selectivity and Conductance Comments
TRPA1 exhibits conductance of 98pS in physiological solution, dependent on Ca2+ and Mg2+ concentration [95].
Voltage Dependence Comments
Voltage-dependence not yet described, inactivation by extracellular Ca2+ might be voltage dependent [95].
Chemical activators (Human)
Isothiocyanates (covalent) and 1,4-dihydropyridines (non-covalent)
Oxidative stress compounds (Mouse)
4-oxo-nonenal: pEC50 5.7, H2O2 : pEC50 3.6  [3,119]
Physical activators (Human)
Cooling (<17°C) (disputed)  [61,95,141]

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
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
methyl salicylate Mm Agonist - - 6x10-4 Physiological 8
Conc range: 6x10-4 M [8]
Holding voltage: Physiological
icilin Mm Agonist - - 1x10-4 Physiological 127
Conc range: 1x10-4 M non-covalent [127]
Holding voltage: Physiological
JT010 Hs Activation 9.2 pEC50 - - 131
pEC50 9.2 (EC50 6.5x10-10 M) [131]
Description: Ligand-induced calcium influx in TRPA1-transfected HEK293 cells.
PF-4840154 Hs Activation 7.6 pEC50 - - 118
pEC50 7.6 This compound has similar activity at rat and mouse TRPA1 [118]
Description: Calcium imaging
Conditions: HEK-293cells expressing TRPA1
dibenzoxazepine Hs Activation 7.2 pEC50 - - 25
pEC50 7.2 [25]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4.
morphanthridine Hs Activation 7.1 pEC50 - - 25
pEC50 7.1 [25]
Description: Patch clamp
Conditions: HEK293 cells expressing human TRPA1
1'-acetoxychavicol acetate Hs Activation 6.8 pEC50 - - 97
pEC50 6.8 [97]
Description: FlexStation 2 Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4
chlorobenzylidene malononitrile Hs Activation 6.7 pEC50 - - 25
pEC50 6.7 (EC50 1.99x10-7 M) covalent [25]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4.
chloropicrin Hs Activation 6.7 pEC50 - - 18
pEC50 6.7 This compound also activates mouse TRPA1 [18]
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 - - 25
pEC50 6.6 [25]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4.
NPPB Hs Activation 6.5 pEC50 - - 79
pEC50 6.5 [79]
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
polygodial Hs Activation 6.4 pEC50 - - 43
pEC50 6.4 (EC50 4x10-7 M) [43]
isovelleral Hs Activation 6.3 pEC50 - - 43
pEC50 6.3 This compound is also an activator of mouse TRPA1. [43]
Description: Calcium imaging
Conditions: HEK293 cells expressing human or mouse TRPA1
ASP7663 Mm Activation 6.3 pEC50 - - 69
pEC50 6.3 (EC50 5x10-7 M) [69]
Description: Ligand-induced increase in intracellular Ca2+ in HEK293 cells expressing mTrpa1.
ASP7663 Hs Activation 6.3 pEC50 - - 69
pEC50 6.3 (EC50 5.1x10-7 M) [69]
Description: Ligand-induced increase in intracellular Ca2+ in HEK293 cells expressing hTRPA1.
ASP7663 Rn Activation 6.3 pEC50 - - 69
pEC50 6.3 (EC50 5.4x10-7 M) [69]
Description: Ligand-induced increase in intracellular Ca2+ in HEK293 cells expressing rTrpa1.
Cu2+ Mm Activation 6.2 pEC50 - - 4,92
pEC50 6.2 (EC50 6x10-7 M) [4,92]
super cinnamaldehyde Mm Activation 6.1 pEC50 - - 82
pEC50 6.1 (EC50 8x10-7 M) [82]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: CHO cells expressing mouse TRPA1
bromoacetone Hs Activation 6.0 pEC50 - - 18
pEC50 6.0 This compound also activates mouse TRPA1 [18]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2dorsal root ganglion neurons
auranofin Hs Activation 6.0 pEC50 - - 55
pEC50 6.0 [55]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fura-2
allicin Mm Agonist 5.9 pEC50 - Physiological 83
pEC50 5.9 [83]
Holding voltage: Physiological
Cu2+ Hs Activation 5.9 pEC50 - - 4,92
pEC50 5.9 (EC50 1.3x10-6 M) [4,92]
Description: Sodium imaging
Conditions: CHO cells expressing human TRPA1
Cd2+ Hs Activation 5.8 pEC50 - - 4,92
pEC50 5.8 (EC50 1.4x10-6 M) [4,92]
Description: Sodium and calcium imaging
Conditions: CHO cells expressing human TRPA1 and mouse dorsal root ganglion neurons
artepillin C Hs Activation 5.7 pEC50 - - 53
pEC50 5.7 (EC50 1.8x10-6 M) [53]
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 - - 134
pEC50 5.7 This compound has a similar activity at mouse TRPA1 [134]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse trigeminal and vagal neurons loaded with Fura-2
Cd2+ Mm Activation 5.7 pEC50 - - 4,92
pEC50 5.7 (EC50 2.1x10-6 M) [4,92]
1,6-hexamethylene diisocyanate Hs Activation 5.6 pEC50 - - 18
pEC50 5.6 This compound also activates mouse TRPA1 [18]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2
N-acetyl-4-benzoquinoneimine Rn Activation 5.6 pEC50 - - 2,100
pEC50 5.6 This compound has similar activity at human and mouse TRPA1 [2,100]
Description: Calcium imaging
Conditions: CHO or HEK293 cells expressing rat/mouse/human TRPA1 loaded with Fura-2
oleocanthal Hs Activation 5.6 pEC50 - -60.0 113
pEC50 5.6 [113]
Holding voltage: -60.0 mV
Description: Patch clamp
Conditions: HEK-293 cells expressing human TRPA1
O3 Hs Activation 5.5 pEC50 - - 135
pEC50 5.5 Ozone has similar activity at mouse TRPA1 [135]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse vagal neurons loaded with Fura-2
2-pentenal ? Activation 5.3 pEC50 - - 11
pEC50 5.3 (EC50 5x10-6 M) [11]
acrolein Hs Agonist 5.3 pEC50 - Physiological 13
pEC50 5.3 (EC50 5.011x10-6 M) covalent [13]
Holding voltage: Physiological
salirasib Hs Activation 5.3 pEC50 - - 86
pEC50 5.3 [86]
Description: FLIPR calcium-influx assay
Conditions: CHO-TREx cells loaded with Fluo-3
apomorphine Hs Activation 5.1 pEC50 - - 121
pEC50 5.1 Apomorphine blocks TRPA1 at 100µM [121]
Description: Calcium imaging, patch clamp
Conditions: HEK293 cells transfected with human TRPA1
allicin Hs Agonist 5.1 pEC50 - Physiological 14
pEC50 5.1 (EC50 7.943x10-6 M) covalent [14]
Holding voltage: Physiological
allyl isothiocyanate Rn Activation 5.0 pEC50 - -40.0 61
pEC50 5.0 [61]
Holding voltage: -40.0 mV
Δ9-tetrahydrocannabinol Hs Agonist 4.9 pEC50 - -60.0 61
pEC50 4.9 (EC50 1.259x10-5 M) non-covalent [61]
Holding voltage: -60.0 mV
benzyl bromide Hs Activation 4.9 pEC50 - - 18
pEC50 4.9 This compound also activates mouse TRPA1 [18]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2
nicotine Hs Activation 4.8 pEC50 - -75.0 133
pEC50 4.8 (EC50 1.7x10-5 M) non-covalent [133]
Holding voltage: -75.0 mV
Description: Patch clamp
Conditions: CHO cells expressing mouse or human TRPA1
allyl isothiocyanate Mm Activation 4.7 pEC50 - Physiological 8
pEC50 4.7 [8]
Holding voltage: Physiological
thymol Hs Activation 4.7 pEC50 6.25x10-6 - 2.5x10-5 - 77
pEC50 4.7 (EC50 2x10-5 M) Conc range: 6.25x10-6 - 2.5x10-5 M non-covalent [77]
Description: FLIPR calcium influx assay
Conditions: Human TRPA1-HEK293 stable cell line loaded with calcium 3 dye
URB597 Hs Agonist 4.6 pEC50 - - 105
pEC50 4.6 (EC50 2.4x10-5 M) non-covalent [105]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: HEK293 cells expressing human TRPA1
4-hydroxynonenal Rn Activation 4.6 pEC50 - - 85,138
pEC50 4.6 [85,138]
Description: Calcium imaging
Conditions: Rat dorsal root ganglion neurons
prostaglandin A2 Mm Activation 4.6 pEC50 - - 87
pEC50 4.6 [87]
Description: Calcium imaging
Conditions: 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
methyl isocyanate Hs Activation 4.6 pEC50 - - 18
pEC50 4.6 This compound also activates mouse TRPA1 [18]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglion neurons loaded with Fura-2
dibutyl phthalate Hs Activation 4.6 pEC50 - - 123
pEC50 4.6 [123]
Description: Calcium imaging
Conditions: CHO cells stably expressing human TRPA1 loaded with Fluo-4
docosahexaenoic acid Rn Activation 4.4 pEC50 - -60.0 93
pEC50 4.4 This compound has similar activity at human and mouse TRPA1 [93]
Holding voltage: -60.0 mV
Description: Patch clamp
Conditions: HEK293 celss expressing rat TRPA1
(-)-menthol Hs Partial agonist 4.0 – 4.5 pEC50 - - 62,149
pEC50 4.0 – 4.5 (EC50 9.5x10-5 – 2.84x10-5 M) Menthol is also active at the mouse TRPA1, but becomes inhibitory at >100µM [62,149]
Description: Calcium imaging, patch clamp
Conditions: CHO cells expressing human TRPA1
methylglyoxal Hs Activation 2.5 – 6.0 pEC50 - - 28,38,68
pEC50 2.5 – 6.0 This compound has similar activity at mouse and rat TRPA1 [28,38,68]
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 59
pEC50 3.8 [59]
Holding voltage: -100.0 mV
Description: Two electrode voltage clamp
Conditions: Xenopus oocytes expressing rat TRPA1
isoflurane Rn Activation 3.7 pEC50 - - 88
pEC50 3.7 [88]
Description: Patch clamp
Conditions: HEK293 cells expressing rat TRPA1
H2O2 Mm Activation 3.6 pEC50 - - 3,119
pEC50 3.6 [3,119]
Description: Calcium imaging
Conditions: CHO cells expressing mouse TRPA1 loaded with Fura-2
2-iodoacetamide Mm Activation 3.5 pEC50 - - 82
pEC50 3.5 (EC50 3.57x10-4 M) [82]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: CHO cells expressing mouse TRPA1
formalin Mm Activation 3.4 pEC50 - - 85,89
pEC50 3.4 (EC50 3.981x10-4 M) covalent. This level of activity is also observed for rat TRPA1 [85,89]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4
niflumic acid Rn Activation 3.3 pEC50 - -100.0 59
pEC50 3.3 [59]
Holding voltage: -100.0 mV
Description: Two electrode voltage clamp
Conditions: Xenopus oocytes expressing rat TRPA1
acetaldehyde Mm Activation 2.9 pEC50 - - 9
pEC50 2.9 [9]
Description: Calcium imaging
Conditions: HEK293 cells expressing mouse TRPA1loaded with Fluo-3
NaHS Mm Activation 2.9 pEC50 - - 129
pEC50 2.9 This compound has similar activity at the human TRPA1 [129]
Description: Calcium imaging
Conditions: HEK293 cells expressing mouse TRPA1 loaded with Fura-2
MTSEA Mm Activation 2.8 pEC50 - - 82
pEC50 2.8 (EC50 1.58x10-3 M) [82]
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 47
pEC50 2.4 [47]
Holding voltage: -60.0 mV
Description: Patch clamp
Conditions: HEK293 cells expressing mouse TRPA1
Zn2+ Mm Activation 2.3 pEC50 - - 4,58
pEC50 2.3 Zinc has similar activity at the human TRPA1 [4,58]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 and mouse dorsal root ganglia neurons loaded with Fura-2
NH4Cl Mm Activation 2.0 pEC50 - - 48
pEC50 2.0 [48]
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 [56], activated by bradykinin [8,13,61], probably activated by noxious cold [8,127], but this is disputed [61,95], mechano-activation is still under discussion. TRPA1 is modulated by intra- and extracellular Ca2+ [95].

Snake and fly TRPA1 are a heat-activated channels [49,104,143].

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 [136].

Further compounds which are reported to activate TRPA1 in vitro include: 2-pentenal (mouse) [13], clotrimazole (human and mouse) [91], WIN55212-2 (mouse) [1] and AM1241 (mouse) [1], sodium hypochlorite (NaOCl; mouse and human) [19], 5,6-EET (mouse) [124], hepoxilin A3 (mouse, rat) [51], 12S-HPETE (mouse, rat) [51], carbon dioxide (rat, mouse) [145], acetic, propinoic, formic, and lactic acids (human, rat, mouse) [144].
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
AM-0902 Rn Antagonist 7.6 pIC50 - - 120
pIC50 7.6 (IC50 2.4x10-8 M) [120]
Description: Antagonism of activator-induced calcium flux measuring 45Ca2+.
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
resolvin D2 Mm Inhibition 8.7 pIC50 - -60.0 109
pIC50 8.7 [109]
Holding voltage: -60.0 mV
Description: Patch-clamp
Conditions: Mouse DRG neurons, mustard oil AITC (300 µM)
resolvin D1 Mm Inhibition 7.2 pIC50 - - 10,109
pIC50 7.2 [10,109]
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 - - 31
pIC50 7.2 This compoud also acts as a gating inhibitor at the rat and mouse TRPA1. [31]
Description: Calcium imaging
Conditions: HEK-293F cells expressing TRPA1
AP18 Hs Inhibition 5.5 pIC50 - - 112
pIC50 5.5 (IC50 3.1x10-6 M) [112]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
Conditions: CHO cells expressing human TRPA1
AP18 Mm Inhibition 5.3 pIC50 - - 112
pIC50 5.3 (IC50 4.5x10-6 M) [112]
Description: Fluorometric Imaging Plate Reader (FLIRP) calcium-influx assay
gentamicin Mm Antagonist 5.2 pIC50 - -80.0 95
pIC50 5.2 [95]
Holding voltage: -80.0 mV
HC030031 Hs Inhibition 5.2 pIC50 - - 89
pIC50 5.2 [89]
Description: Calcium imaging
Conditions: HEK293 cells expressing human TRPA1 loaded with Fluo-4
isopentenyl diphosphate Mm Inhibition 5.1 pIC50 - - 10
pIC50 5.1 [10]
Description: Calcium imaging
Conditions: HEK-293 cells expressing TRPA1
TCS 5861528 Hs Inhibition 4.8 pIC50 - - 146
pIC50 4.8 [146]
Description: Calcium imaging
Conditions: Human TRPA1-inducible HEK-293 cells (HEK-LacltrpA1 clone B22), Aallyl isothiocyanate as agonist
camphor Mm Antagonist 4.2 pIC50 - Physiological 84
pIC50 4.2 [84]
Holding voltage: Physiological
(-)-menthol Mm Antagonist 4.2 pIC50 - Physiological 84
pIC50 4.2 [84]
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 Value Parameter Concentration range (M) Holding voltage (mV) Reference
AM-0902 Hs Antagonist 7.7 pIC50 - - 120
pIC50 7.7 (IC50 2x10-8 M) [120]
Description: Antagonism of activator-induced calcium flux measuring 45Ca2+.
Gd3+ Mm Antagonist 7.0 pIC50 - -80.0 95
pIC50 7.0 [95]
Holding voltage: -80.0 mV
ruthenium red Mm Inhibition 5.5 pIC50 - -80.0 95
pIC50 5.5 (IC50 3.55x10-6 M) [95]
Holding voltage: -80.0 mV
amiloride Mm Inhibition 3.3 pIC50 - -80.0 95
pIC50 3.3 [95]
Holding voltage: -80.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
Blocking effects are modulated by divalent cations [95].
Immunopharmacology Comments
Several lines of evidence implicate TRPA1 in inflammation, inflammatory pain and inflammatory diseases [73,81,90,111,128,151].
Cell Type Associations
Immuno Cell Type:  Mast cells
Comment:  TRPA1 is reported to be involved mast cell secretory granule formation in rat.
References:  108
Tissue Distribution
Brain, heart, small intestine, lung, skeletal muscle, and pancreas.
Species:  Human
Technique:  Northern Blot
References:  126
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:  70,106,114,116
Skin cells (including fibroblasts, keratinocytes and melanocytes).
Species:  Human
Technique:  RT-PCR, Western blot, calcium imaging
References:  16,26,139
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:  50,129
Odontoblast and dental pulp fibroblasts.
Species:  Human
Technique:  RT-PCR, immunohistochemistry, calcium imaging and Western blot.
References:  40-41
Synoviocyte
Species:  Human
Technique:  RT-PCR
References:  54
Respiratory system: including lung fibroblasts, airway epithelial and smooth muscle cells
Species:  Human
Technique:  RT-PCR, western blot, immunocytochemistry
References:  94,102
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:  14,32,61,67,95,127
Jugular/nodose ganglion neurons
Species:  Mouse
Technique:  RT-PCR
References:  98
Olfactory epithelium
Species:  Mouse
Technique:  Immunohistochemistry
References:  96
Nerve fibers innervating the vestibular sensory cells.
Species:  Mouse
Technique:  Immunohistochemistry
References:  132
Endothelial cells from cerebral arteries.
Species:  Rat
Technique:  RT-PCR
References:  37
Pancreatic beta cells.
Species:  Rat
Technique:  RT-PCR, immunocytochemistry, western blotting
References:  28
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:  32,61,95,127
Physiological Functions
Colitis
Species:  Mouse
Tissue:  Colon
References:  42
Senses various noxious stimuli: pungent natural compounds, noxious cold temperature, environmental irritants, inflammatory peptides, noxious mechanical stimuli.
Species:  Mouse
Tissue:  Sensory neurones.
References:  110
Bladder overaction (due to spinal cord injury and bladder hyperreflexia, afferent transduction).
Species:  Rat
Tissue:  Bladder and dorsal root ganglion neurons.
References:  5,36
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:  37,74,101,115
Insulin release
Species:  Rat
Tissue:  Pancreatic beta cells
References:  28
Cough; observed in human, guinea pig and mouse.
Species:  Human
Tissue:  Vagus nerve
References:  7,21
Facilitating excitatory synaptic transmission.
Species:  Rat
Tissue:  Substantia gelatinosa neurons
References:  71
Sense hyperoxia and hypoxia
Species:  Mouse
Tissue:  Nodose ganglion and dorsal root ganglia neurons.
References:  130
Regulation of gastrointestinal motility. Note that this has also been described in guinea pig.
Species:  Mouse
Tissue:  Ileum, colon and myenteric neurons.
References:  106,114
Itch
Species:  Mouse
Tissue:  Dorsal root ganglia neurons, skin
References:  45,78,80,147-148
Visceral nociception
Species:  Mouse
Tissue:  Dorsal root ganglia neurons innervating the colon.
References:  29
Pancreatic inflammation and pain
Species:  Mouse
Tissue:  Pancreatic nerve fibers and dorsal root ganglia neurons innervating the pancreas.
References:  30,122
Allergic asthma and non-allergic airway hyperreactivity. Observed in mouse and rat.
Species:  Mouse
Tissue:  Airway
References:  27,57,117
Melanin synthesis
Species:  Human
Tissue:  Skin
References:  16
Inflammatory and neuropathic pain (reported in rat and mouse)
Species:  Rat
Tissue: 
References:  22,33-34,39,103,107,137
Allergic contact dermatitis
Species:  Mouse
Tissue:  Dorsal root ganglion neurons
References:  78,123
Mechanosensation and mechanical transduction.
Species:  Mouse
Tissue:  Sensory neurons, skin, colon and nerve.
References:  23-24,76,142
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:  13,34-35,44,63,75,127
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:  65
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:  110
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:  15,17
Phenotypes, Alleles and Disease Models Mouse data from MGI

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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:  Episodic pain syndrome, familial, 1; FEPS1
Description: An autosomal-dominant familial episodic pain syndrome characterized by episodes of debilitating upper body pain, triggered by fasting and physical stress.
Synonyms: Familial episodic pain syndrome [Orphanet: ORPHA391384]
Familial episodic pain syndrome with predominantly upper body involvement [Orphanet: ORPHA391389]
OMIM: 615040
Orphanet: ORPHA391389, ORPHA391384
References:  72
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