INT127499

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Context Info
Confidence 0.70
First Reported 2005
Last Reported 2010
Negated 2
Speculated 1
Reported most in Body
Documents 72
Total Number 84
Disease Relevance 21.70
Pain Relevance 26.86

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

Anatomy Link Frequency
neurons 7
pore 5
synovial fluid 2
internal 1
bladder 1
TRPA1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Pain 877 100.00 Very High Very High Very High
TRP channel 254 100.00 Very High Very High Very High
nociceptor 29 100.00 Very High Very High Very High
qutenza 118 99.96 Very High Very High Very High
Inflammation 293 99.82 Very High Very High Very High
antagonist 1165 99.80 Very High Very High Very High
Potency 122 99.66 Very High Very High Very High
imagery 87 99.52 Very High Very High Very High
agonist 1001 99.44 Very High Very High Very High
allodynia 64 99.24 Very High Very High Very High
Disease Link Frequency Relevance Heat
Frostbite 5 99.90 Very High Very High Very High
Neurogenic Inflammation 130 99.82 Very High Very High Very High
Nociception 55 99.52 Very High Very High Very High
Pain 940 99.26 Very High Very High Very High
INFLAMMATION 205 99.24 Very High Very High Very High
Neuropathic Pain 142 99.24 Very High Very High Very High
Fever 1 98.22 Very High Very High Very High
Targeted Disruption 312 98.18 Very High Very High Very High
Hyperalgesia 224 95.32 Very High Very High Very High
Ganglion Cysts 51 94.80 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Here we show that intracellular Ca(2+) activates human TRPA1 via an EF-hand domain and that cold sensitivity occurs indirectly (and nonphysiologically) through increased [Ca(2+)](i) during cooling in heterologous systems.
Positive_regulation (activates) of TRPA1
1) Confidence 0.70 Published 2007 Journal Nat. Neurosci. Section Abstract Doc Link 17259981 Disease Relevance 0 Pain Relevance 0.09
Functional characterization of site-directed cysteine mutants of TRPA1 in combination with labeling experiments using biotinylated 15d-PGJ(2) demonstrated that modifications of cytoplasmic N-terminal cysteines (Cys421 and Cys621) were responsible for the activation of TRPA1 by 15d-PGJ(2).
Positive_regulation (activation) of TRPA1
2) Confidence 0.70 Published 2008 Journal Channels (Austin) Section Abstract Doc Link 18769139 Disease Relevance 0.52 Pain Relevance 0.41
Activation of TRPA1 by environmental irritants such as mustard oil, allicin and acrolein causes acute pain.
Positive_regulation (Activation) of TRPA1 associated with acute pain
3) Confidence 0.70 Published 2008 Journal Channels (Austin) Section Abstract Doc Link 18769139 Disease Relevance 0.50 Pain Relevance 0.28
Here, we show that a variety of inflammatory mediators (15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), nitric oxide (NO), hydrogen peroxide (H(2)O(2)), and proton (H(+))) activate human TRPA1 heterologously expressed in HEK cells.
Positive_regulation (activate) of TRPA1 associated with inflammatory mediators
4) Confidence 0.70 Published 2008 Journal Channels (Austin) Section Abstract Doc Link 18769139 Disease Relevance 0.53 Pain Relevance 0.31
However, the endogenous ligands that directly activate TRPA1 remain elusive in inflammation.
Positive_regulation (activate) of TRPA1 associated with inflammation
5) Confidence 0.70 Published 2008 Journal Channels (Austin) Section Abstract Doc Link 18769139 Disease Relevance 0.54 Pain Relevance 0.31
We have also characterized noxious cold response of these cell lines and show that noxious cold activates both human and rat TRPA1.
Positive_regulation (activates) of TRPA1
6) Confidence 0.69 Published 2007 Journal Mol Pain Section Abstract Doc Link PMC2222611 Disease Relevance 0.46 Pain Relevance 0.61
TRPA1 is activated by numerous reactive compounds making it a sensor for reactive compounds in the body.
Positive_regulation (activated) of TRPA1 in body
7) Confidence 0.69 Published 2007 Journal Mol Pain Section Abstract Doc Link PMC2222611 Disease Relevance 0.55 Pain Relevance 0.62
In agreement with this hypothesis, recently, it was reported that 4-hydroxynonenal, an endogenous aldehyde causes pain and neurogenic inflammation through activation of TRPA1 [14].
Positive_regulation (activation) of TRPA1 associated with pain, inflammation and neurogenic inflammation
8) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0.59 Pain Relevance 0.45
Since selective antagonists of TRPA1 potently inhibited noxious cold-induced 45Ca2+ uptake into CHO cells expressing TRPA1, we believe that noxious cold does activate TRPA1.
Positive_regulation (activate) of TRPA1 associated with antagonist
9) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.18
Since these compounds are capable of forming covalent adducts with thiols, other reactive compounds such as acrolein, iodo-acetamide, N-methylmaleimide, and several others were evaluated and shown to activate TRPA1 through reversible covalent modification of cystenies in the intracellular loops of TRPA1 [8-11].
Positive_regulation (activate) of TRPA1
10) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0.46 Pain Relevance 0.41
We believe these results were confounded by the nature of AITC activation of TRPA1, which acts by covalent modification of intracellular cysteines to activate the TRPA1 channels [8].
Positive_regulation (activation) of TRPA1
11) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.17
Since we cannot completely rule out the contribution of calcium directly activating TRPA1 channels during noxious cold application, it is possible that both calcium and noxious cold might have contributed to TRPA1 activation and concomitant 45Ca2+ uptake in our studies.
Positive_regulation (activating) of TRPA1
12) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.17
Recently, it was reported that calcium directly activates TRPA1 channels [28,29].
Positive_regulation (activates) of TRPA1
13) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.29
Next, we evaluated the ability of ruthenium red to inhibit noxious cold activation of TRPA1 (Fig. 2E).
Positive_regulation (activation) of TRPA1
14) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.07
All four TCEB compounds' did not induce any calcium uptake through activation of TRPA1 in these assays, suggesting that these are not partial agonists of TRPA1 (Fig. 3A–D).
Positive_regulation (activation) of TRPA1 associated with agonist
15) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.15
In summary, these studies confirm that both human and rat TRPA1 are activated by AITC and noxious cold and a pore blocker, ruthenium red inhibits both.
Positive_regulation (activated) of TRPA1 in pore
16) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.17
Two most potent TCEB compounds at inhibiting AITC activation of human TRPA1 in both aequorin based luminescence and electrophysiology assays were AMG9090 and AMG2504.
Positive_regulation (activation) of TRPA1
17) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.07
As reported previously, both human and rat TRPA1 are activated by AITC and inhibited by ruthenium red.
Positive_regulation (activated) of TRPA1
18) Confidence 0.69 Published 2007 Journal Mol Pain Section Abstract Doc Link PMC2222611 Disease Relevance 0.50 Pain Relevance 0.62
Cold activation of TRPA1 was followed as a function of cellular uptake of radioactive calcium (45Ca2+, Perkin Elmer).
Positive_regulation (activation) of TRPA1
19) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.33
Based on the structures of TCEB compounds, un-substituted phenyl on the amide seems to give greater potency to inhibit AITC activation of human TRPA1.
Positive_regulation (activation) of TRPA1 associated with potency
20) Confidence 0.69 Published 2007 Journal Mol Pain Section Body Doc Link PMC2222611 Disease Relevance 0 Pain Relevance 0.36

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