INT354207

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Context Info
Confidence 0.52
First Reported 2010
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 1
Total Number 11
Disease Relevance 6.55
Pain Relevance 3.24

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

transport (Accn3) extracellular space (Igfbp7) extracellular region (Igfbp7)
cell adhesion (Igfbp7) plasma membrane (Accn3) cytoplasm (Accn3)
Anatomy Link Frequency
neuronal 1
Igfbp7 (Mus musculus)
Accn3 (Mus musculus)
Pain Link Frequency Relevance Heat
Neuronal excitability 33 98.04 Very High Very High Very High
Inflammation 187 96.36 Very High Very High Very High
ischemia 44 95.24 Very High Very High Very High
Pain 143 94.68 High High
PcTx1 22 92.44 High High
ASIC 165 82.76 Quite High
Inflammatory response 11 82.00 Quite High
agonist 22 79.32 Quite High
nMDA receptor 11 78.32 Quite High
IPN 77 76.80 Quite High
Disease Link Frequency Relevance Heat
Acidosis 154 100.00 Very High Very High Very High
Aids-related Complex 88 100.00 Very High Very High Very High
Cancer 22 97.44 Very High Very High Very High
Injury 33 96.96 Very High Very High Very High
Infection 33 96.64 Very High Very High Very High
INFLAMMATION 209 96.36 Very High Very High Very High
Coronary Artery Disease 22 95.56 Very High Very High Very High
Pain 132 94.68 High High
Inflammatory Pain 77 76.80 Quite High
Cv Unclassified Under Development 22 76.28 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Next we asked how AGM activates ASIC3 channels in a manner similar to GMQ, given the difference in their structural flexibility (linear AGM vs. circular GMQ with a heterocycle, Figure 1A) [10].
AGM Positive_regulation (activates) of ASIC3
1) Confidence 0.52 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.14 Pain Relevance 0.06
Therefore, AGM not only activates ASIC3 by itself at normal pH (Figure 1; Ref. [10]), but also exerts positive cooperative effect when administrated with other inflammatory factors such as mild acidosis, hyperosmolarity, and AA, further strengthening the notion that ASIC3 channels act as a multiple sensor to integrate diverse signals present in the pathophysiological environment [8,9].


AGM Positive_regulation (activates) of ASIC3 associated with acidosis and inflammation
2) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.48 Pain Relevance 0.28
In a previous study, we have shown that extracellular AGM and its structural analog ARC (Figure 1A) activate ASIC3 at neutral pH [10].
AGM Positive_regulation (activate) of ASIC3 associated with aids-related complex
3) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.98 Pain Relevance 0.42
We found that AGM activated ASIC3 channels regardless the presence or absence of extracellular Ca2+ (data not shown).
AGM Positive_regulation (activated) of ASIC3
4) Confidence 0.38 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.16 Pain Relevance 0.08
In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance.
AGM Positive_regulation (activated) of ASIC3
5) Confidence 0.35 Published 2010 Journal Mol Pain Section Abstract Doc Link PMC3017031 Disease Relevance 0.45 Pain Relevance 0.23
The fact that AGM directly activates ASIC3 channels [10] prompted us to look for the effects of polyamines and other arginine metabolites [11] (Figure 1A).
AGM Positive_regulation (activates) of ASIC3
6) Confidence 0.35 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.93 Pain Relevance 0.32
In this study, we further showed that AGM-induced activation of ASIC3 is profoundly potentiated by mild acidosis, hyperosmolarity, increased arachidonic acid (AA), or reduced extracellular Ca2+, conditions that occur during inflammation and many other pathophysiological processes [8,33-39].
AGM-induced Positive_regulation (activation) of ASIC3 associated with acidosis and inflammation
7) Confidence 0.35 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.98 Pain Relevance 0.42
Together, these data strongly support that activation of ASIC3 by AGM relies on polar, steric, and electrostatic interactions with the nonproton ligand sensing domain in the channel [10], regardless whether the ligand is linear and flexible (i.e.
AGM Positive_regulation (activation) of ASIC3
8) Confidence 0.35 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.12 Pain Relevance 0.15
Interestingly, AGM caused further increase over the current induced by the combination of pH 7.0 and hyperosmolarity (Figure 3), suggesting that AGM, mild acidosis, and hyperosmolarity act synergically to facilitate ASIC3 opening, which may explain the enhanced sensory neuronal excitability under conditions of inflammation [8] or cardiac ischemia [36].


AGM Positive_regulation (facilitate) of ASIC3 in neuronal associated with coronary artery disease, acidosis, inflammation, neuronal excitability and ischemia
9) Confidence 0.33 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.69 Pain Relevance 0.43
The inability of AGM pretreatment to enhance ASIC3 response to mild acidosis (Figure 2D, E, panel II) suggests a novel mechanism underlying the observed synergy between H+ and AGM that differs from the allosteric effect of tarantula toxin psalmotoxin 1 (PcTX1) on ASIC1 channels [44,45].
AGM Positive_regulation (enhance) of ASIC3 associated with acidosis and pctx1
10) Confidence 0.33 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.72 Pain Relevance 0.49
At a concentration of 1 mM, only AGM and its analog ARC (Figure 1B), but not polyamines (including spermine, spermidine, and putrescine), nor L-arginine, nor L-ornithine, were able to activate the ASIC3 channel at pH 7.4.
AGM Positive_regulation (activate) of ASIC3 associated with aids-related complex
11) Confidence 0.30 Published 2010 Journal Mol Pain Section Body Doc Link PMC3017031 Disease Relevance 0.90 Pain Relevance 0.35

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