INT122053

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Context Info
Confidence 0.69
First Reported 2004
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 16
Total Number 29
Disease Relevance 13.02
Pain Relevance 11.98

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

signal transduction (P2rx4) transport (P2rx4) plasma membrane (P2rx4)
Anatomy Link Frequency
C8-B4 10
microglia 3
macrophages 1
spinal 1
spinal cord 1
P2rx4 (Mus musculus)
Pain Link Frequency Relevance Heat
Pain 83 100.00 Very High Very High Very High
neuralgia 4 100.00 Very High Very High Very High
Lasting pain 41 99.62 Very High Very High Very High
antidepressant 490 99.52 Very High Very High Very High
Brush evoked pain 51 99.16 Very High Very High Very High
Neuropathic pain 240 98.76 Very High Very High Very High
Peripheral nerve injury 13 98.52 Very High Very High Very High
Spinal cord 39 98.28 Very High Very High Very High
IPN 18 98.08 Very High Very High Very High
antagonist 90 97.08 Very High Very High Very High
Disease Link Frequency Relevance Heat
Nervous System Injury 107 99.64 Very High Very High Very High
Pain 142 99.62 Very High Very High Very High
Neuropathic Pain 365 99.16 Very High Very High Very High
Inflammatory Pain 18 98.08 Very High Very High Very High
INFLAMMATION 65 96.44 Very High Very High Very High
Hypersensitivity 26 93.96 High High
Ganglion Cysts 19 90.60 High High
Injury 21 84.40 Quite High
Pressure And Volume Under Development 13 81.76 Quite High
Disease 5 77.04 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This increase in P2X4 function was concomitant with higher receptor protein expression, itself related to an upregulation of P2X4 mRNA levels that peaked at 48 h post-LPS treatment.
Positive_regulation (upregulation) of P2X4
1) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17675190 Disease Relevance 0.26 Pain Relevance 0.17
This increase in P2X4 function was concomitant with higher receptor protein expression, itself related to an upregulation of P2X4 mRNA levels that peaked at 48 h post-LPS treatment.
Positive_regulation (increase) of P2X4
2) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17675190 Disease Relevance 0.27 Pain Relevance 0.18
Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain.
Positive_regulation (Up-regulation) of P2X4 in spinal associated with neuralgia, nervous system injury, neuropathic pain and peripheral nerve injury
3) Confidence 0.67 Published 2008 Journal J. Neurosci. Section Title Doc Link 18971468 Disease Relevance 0.81 Pain Relevance 1.22
Stimulation of P2X4R in microglia induces release of brain-derived neurotrophic factor [9,22,23], a factor that is crucial for producing aberrant excitability of dorsal horn neurons [9,24].
Positive_regulation (Stimulation) of P2X4R in dorsal horn associated with dorsal horn neuron
4) Confidence 0.61 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704200 Disease Relevance 1.63 Pain Relevance 0.93
To explore this possibility, we used surface biotinylation and found increased levels of P2X4 protein in the membranes of activated C8-B4 cells, which may explain the increase in peak currents observed during C8-B4 cell activation (Table I) or when lysosomal secretion was triggered by MA (Qureshi et al., 2007).
Positive_regulation (increased) of P2X4 protein in C8-B4
5) Confidence 0.60 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0.06 Pain Relevance 0.12
However, our data do not rule out the possibility of elevated total P2X4 protein levels over longer periods of microglial activation (Raouf et al., 2007).
Positive_regulation (elevated) of P2X4 protein
6) Confidence 0.60 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0
We found no evidence to suggest that the significant increase in P2X4 mRNA also measured in activated C8-B4 cells led to elevated levels of P2X4 proteins (Table I).
Positive_regulation (increase) of P2X4 mRNA in C8-B4
7) Confidence 0.60 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0
Fifth, C8-B4 cell activation results in up-regulation of P2X4 transcripts, but this is not associated with any measurable increase in total P2X4 protein levels.
Positive_regulation (increase) of P2X4 protein in C8-B4
8) Confidence 0.60 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0.06 Pain Relevance 0.32
In principle, the increased P2X4 mRNAs (Fig. 3) could explain why ATP-evoked currents in C8-B4 cells were increased during the activated state.
Positive_regulation (increased) of P2X4 in C8-B4
9) Confidence 0.60 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0
Treatment of BV-2 cells with LPS leads to a transient increase in ivermectin-sensitive P2X4 currents, while dominant P2X7 currents remain largely unaffected.
Positive_regulation (increase) of P2X4
10) Confidence 0.60 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17675190 Disease Relevance 0.29 Pain Relevance 0.19
By using P2X4R-deficient mice, we revealed that P2X4R is not required for all forms of pain responses, but rather is crucial for specialized pain states, namely chronic inflammatory and, in particular, neuropathic pain.
Neg (not) Positive_regulation (required) of P2X4R associated with pain, inflammation and neuropathic pain
11) Confidence 0.50 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704200 Disease Relevance 1.69 Pain Relevance 0.92
Current responses of P2X4 and P2X7 subtypes could be distinguished based on their respective sensitivity to the positive modulator ivermectin and to the antagonist Brilliant Blue G.
Positive_regulation (responses) of P2X4 associated with antagonist
12) Confidence 0.50 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17675190 Disease Relevance 0.33 Pain Relevance 0.21
Using real-time polymerase chain reaction, we found that P2X4 transcripts were increased during the activated state by 2.4-fold, but this increase was not reflected by a parallel increase in total P2X4 proteins.
Positive_regulation (increased) of P2X4
13) Confidence 0.43 Published 2010 Journal The Journal of General Physiology Section Abstract Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0.08
However, of these, only P2X4 transcript levels were significantly increased by 2.4-fold in C8-B4 cells activated (Fig. 3) using conditions that give rise to ATP-evoked inward currents (Fig. 2).


Positive_regulation (increased) of P2X4 in C8-B4
14) Confidence 0.43 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0.05
Pharmacological experiments also revealed some distinctive features of P2X4 receptors: ivermectin (IVM) was an allosteric modulator of P2X4 receptors (Khakh et al., 1999b; Priel and Silberberg, 2004), they were relatively resistant to P2X antagonists (Buell et al., 1996; Jones et al., 2000), and antidepressants reduced P2X4 responses (Nagata et al., 2009).
Positive_regulation (modulator) of P2X4 associated with antidepressant and antagonist
15) Confidence 0.43 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0.09
Why do pre-applications of antidepressants lead to a reduction in P2X4 receptor responses in activated C8-B4 cells (Fig. 12), even though these drugs do not inhibit P2X4 receptors directly (Fig. 11)?
Positive_regulation (responses) of P2X4 in C8-B4 associated with antidepressant
16) Confidence 0.43 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0.50
The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors.
Positive_regulation (used) of P2X4
17) Confidence 0.43 Published 2008 Journal J. Neurophysiol. Section Abstract Doc Link 18509077 Disease Relevance 0.37 Pain Relevance 0.52
Our previous study has implicated Lyn (microglial SFK) as a critical kinase causing P2X4R upregulation [13].
Positive_regulation (upregulation) of P2X4R
18) Confidence 0.41 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704200 Disease Relevance 1.47 Pain Relevance 0.97
Based on the known single-channel properties of P2X4 receptors (Priel and Silberberg, 2004), our data suggest that resting C8-B4 cells have just a few (perhaps <10) P2X4 receptors per cell, and that this number increases to several hundred P2X4 receptors per cell during the activated state.
Positive_regulation (increases) of P2X4 in C8-B4
19) Confidence 0.40 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0.03
We found that cell surface P2X4 receptor levels increased by ?
Positive_regulation (increased) of P2X4
20) Confidence 0.40 Published 2010 Journal The Journal of General Physiology Section Abstract Doc Link PMC2847917 Disease Relevance 0 Pain Relevance 0.15

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