INT121241

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Context Info
Confidence 0.69
First Reported 2004
Last Reported 2009
Negated 0
Speculated 2
Reported most in Body
Documents 65
Total Number 82
Disease Relevance 40.94
Pain Relevance 13.59

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

transport (P2rx7) cell morphogenesis (P2rx7) mitochondrion organization (P2rx7)
protein complex (P2rx7) transmembrane transport (P2rx7) cytoplasm (P2rx7)
Anatomy Link Frequency
macrophages 7
microglia 7
mast cells 4
plasma 2
monocytes 2
P2rx7 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammation 2512 99.92 Very High Very High Very High
Inflammatory mediators 268 99.88 Very High Very High Very High
ischemia 91 99.82 Very High Very High Very High
Action potential 8 99.24 Very High Very High Very High
Neuropathic pain 129 99.00 Very High Very High Very High
rheumatoid arthritis 262 98.94 Very High Very High Very High
agonist 513 98.60 Very High Very High Very High
Inflammatory stimuli 78 98.58 Very High Very High Very High
cytokine 1797 98.44 Very High Very High Very High
medulla 3 98.20 Very High Very High Very High
Disease Link Frequency Relevance Heat
Targeted Disruption 289 99.96 Very High Very High Very High
Infection 243 99.96 Very High Very High Very High
Injury 188 99.96 Very High Very High Very High
INFLAMMATION 3090 99.92 Very High Very High Very High
Atherosclerosis 78 99.90 Very High Very High Very High
Death 728 99.88 Very High Very High Very High
Cv Unclassified Under Development 91 99.82 Very High Very High Very High
Mycobacterial Infection 442 99.76 Very High Very High Very High
Middle Cerebral Artery Infarction 65 99.76 Very High Very High Very High
Amyloid Plaque 39 99.68 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Activation of P2X7 receptors is the mechanism by which ATP stimulates the rapid maturation and release of IL-1beta from macrophages and microglial cells.
Positive_regulation (Activation) of P2X7 in microglial cells
1) Confidence 0.69 Published 2009 Journal Behav. Brain Res. Section Abstract Doc Link 19464323 Disease Relevance 0.53 Pain Relevance 0.55
As ATP can be released upon tissue damage [104] and in response to inflammatory stimuli [49] (both of which may be present in asthma) it is possible that the P2X7R would be activated, resulting in IL-8 production and propagation of the immune response (Figure 3).
Positive_regulation (activated) of P2X7R associated with asthma and inflammatory stimuli
2) Confidence 0.68 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.76 Pain Relevance 0.33
Although the mechanisms of action of the porcine CHDP protegrin-1 and -3 have been shown to be P2X7R-independent [39], three studies have now proposed that P2X7R activation underlies some of the immunomodulatory effects of the human CHDP, LL-37 [38,40,41].
Positive_regulation (activation) of P2X7R
3) Confidence 0.68 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.28 Pain Relevance 0.08
Irrespective, these studies suggest that P2X7R activation might extend the lifespan of PMN at sites of infection and inflammation, and modulate the mechanism of cell death in these cells.
Positive_regulation (activation) of P2X7R associated with inflammation, lifespan, death and infection
4) Confidence 0.68 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.90 Pain Relevance 0.05
has been reported to induce COX-2 in various tissues including glia, it has been proposed that a vicious cycle occurs whereby ATP release (from cell death for example) leads to P2X7R activation, IL-1?
Positive_regulation (activation) of P2X7R associated with death
5) Confidence 0.68 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.09 Pain Relevance 0.20
production in cultured microglial cells through the activation of the P2X7R.
Positive_regulation (activation) of P2X7R in microglial cells
6) Confidence 0.68 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.72 Pain Relevance 0.27
With high concentrations (0.5–5 mM) of ATP required for optimal activation of P2X7R-mediated IL-1?
Positive_regulation (activation) of P2X7R-mediated
7) Confidence 0.68 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.31 Pain Relevance 0.07
secretion from immune cells by controlling activation of P2X7.
Positive_regulation (activation) of P2X7 in immune cells
8) Confidence 0.68 Published 2007 Journal Purinergic Signal Section Body Doc Link PMC2096758 Disease Relevance 0.33 Pain Relevance 0.07
Bulanova et al. [25] have shown that addition of extracellular ATP in the millimolar range induced activation of P2X7 expressed on murine mast cells, resulting in the rapid but transient phosphorylation of ERK, Jak2 and STAT6.
Positive_regulation (activation) of P2X7 in mast cells
9) Confidence 0.68 Published 2007 Journal Purinergic Signal Section Body Doc Link PMC2096758 Disease Relevance 0.43 Pain Relevance 0.13
In brainstem slices from 15 to 26 day old pentobarbitone-anesthetized mice, we examined the effect of P2X7RS activation on excitatory postsynaptic currents (EPSCs) recorded from hypoglossal motoneurons using whole-cell patch clamp techniques.
Spec (examined) Positive_regulation (activation) of P2X7RS in motoneurons associated with medulla
10) Confidence 0.65 Published 2004 Journal Neuroscience Section Abstract Doc Link 15350640 Disease Relevance 0 Pain Relevance 0.13
release induced by P2X7R and panx1 activation.
Positive_regulation (activation) of P2X7R
11) Confidence 0.64 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0 Pain Relevance 0
This model is based on three main observations: (a) activation of P2X7R in macrophages induces K+ depletion [17, 40, 53, 57] as does stimulation with nigericin or maitotoxin; (b) activation of caspase-1 by these stimuli does not occur in high extracellular K+ solution [40, 57–59]; and (c) the in vitro assembly of the inflammasome is dependent on K+ concentrations lower than 70 mM [58].
Positive_regulation (activation) of P2X7R in macrophages
12) Confidence 0.64 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0.07 Pain Relevance 0
Activation of P2X7R by the nucleotide leads to the assembly of a multi-protein complex called the NLRP3 inflammasome that recruits pro-caspase-1 and induces its proteolytic activation (Fig. 3) [53–55].
Positive_regulation (Activation) of P2X7R
13) Confidence 0.64 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0.16 Pain Relevance 0.12
Concentrations of ATP required to activate P2X7R (usually >100 ?
Positive_regulation (activate) of P2X7R
14) Confidence 0.64 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0 Pain Relevance 0.03
However, as described earlier, care must now be taken in interpreting results observed in vivo, as although ATP was originally thought to be the only endogenous agonist of the P2X7R, recently other physiological agents such as LL37 (see above) and NAD [63] have been reported to activate the P2X7R at lower concentrations.
Positive_regulation (activate) of P2X7R associated with agonist
15) Confidence 0.60 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.78 Pain Relevance 0.39
High concentrations of extracellular ATP activates P2X7R ion channel resulting in a cation permeability (Na+ influx/K+ efflux and intracellular Ca++ rise) and the activation of panx1.
Positive_regulation (activates) of P2X7R
16) Confidence 0.56 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0.07 Pain Relevance 0
A more extensive range of potent, selective P2X7R ligands is required for a better understanding of the cascade of cellular processes associated with the P2X7R.
Positive_regulation (required) of P2X7R
17) Confidence 0.49 Published 2007 Journal Curr. Med. Chem. Section Abstract Doc Link 17584060 Disease Relevance 0.37 Pain Relevance 0.46
With P2X7R activation known to be associated with cell death, Lammas et al [127] suggested that the P2X7R may play a role in the apoptosis of infected macrophages and the accompanying mycobacterial death.
Positive_regulation (activation) of P2X7R in macrophages associated with apoptosis and death
18) Confidence 0.49 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.56 Pain Relevance 0.09
Such studies indicate that in addition to extracellular ATP, the endogenous, inducible CHDP, LL-37 may activate the P2X7R on key innate immune effector cells to modulate cytokine release.
Positive_regulation (activate) of P2X7R associated with cytokine
19) Confidence 0.49 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.47 Pain Relevance 0.19
As a result of the importance of the P2X7R in IL-1?
Positive_regulation (importance) of P2X7R
20) Confidence 0.49 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.98 Pain Relevance 0.12

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