INT88327

Context Info Confidence 0.77 First Reported 2000 Last Reported 2010 Negated 4 Speculated 0 Reported most in Body Documents 109 Total Number 110 Disease Relevance 48.86 Pain Relevance 22.41

transport (P2rx7) cell morphogenesis (P2rx7) mitochondrion organization (P2rx7) protein complex (P2rx7) transmembrane transport (P2rx7) cytoplasm (P2rx7)

Anatomy Link Frequency microglial cells 8 macrophages 6 monocytes 4 pore 4 C8-B4 4 P2rx7 (Mus musculus) P2rx7 - E496A (1)

Pain Link Frequency Relevance Heat cytokine 2505 100.00 substance P 6 100.00 antagonist 951 99.96 agonist 622 99.92 Inflammatory response 393 99.76 Central nervous system 57 99.68 Arthritis 178 99.60 Inflammation 3215 99.56 Inflammatory mediators 361 99.56 Thermal hyperalgesia 1 99.32

Disease Link Frequency Relevance Heat Targeted Disruption 433 100.00 Hypersensitivity 179 99.84 Apoptosis 1196 99.72 Death 704 99.64 Arthritis 234 99.60 INFLAMMATION 4001 99.56 Cancer 399 99.52 Neuropathic Pain 527 99.50 Stress 39 99.36 Hyperalgesia 88 99.32

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Protein

Mutation

Event

Anatomy

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Speculation

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Disease term

Upon stimulation by high concentrations of ATP it generates a non-selective membrane pore which is permeable to hydrophilic molecules with molecular weight up to 900 Da. ii) Though its physiological function is yet to be fully understood, there is high P2X7R expression in microglia.

Gene_expression (expression) of P2X7R in microglia

1) Confidence 0.77 Published 2007 Journal Curr. Med. Chem. Section Abstract Doc Link 17584060 Disease Relevance 0.38 Pain Relevance 0.41

release in vitro [38], alternative endogenous agonists that could produce significant P2X7R stimulation have been sought.

Gene_expression (produce) of P2X7R associated with agonist

2) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.35 Pain Relevance 0.08

Recently it was shown that P2X7R transfection increased cellular energy stores (i.e.

Gene_expression (transfection) of P2X7R

3) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.69 Pain Relevance 0.16

In particular, the P2X7 receptor (P2X7R) which is expressed primarily (though not exclusively) on cells of haemopoietic origin [3] is thought to play an important role in macrophage/microglial and granulocyte function by regulating cytokine production and apoptosis.

Neg (not) Gene_expression (expressed) of P2X7 in granulocyte associated with apoptosis and cytokine

4) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.41 Pain Relevance 0.47

These observations are of clear importance given the earlier observation that the P2X7R is over expressed in several cancers [147].

Gene_expression (expressed) of P2X7R associated with cancer

5) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.90 Pain Relevance 0.05

P2X7R expression on human cells has been demonstrated on PMN, HL-60 promyelocytes and granulocytic differentiated cells, and is reported to increase with granulocytic differentiation [100].

Gene_expression (expression) of P2X7R in promyelocytes

6) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.01 Pain Relevance 0.06

This stimulation-dependent expression contrasts with a more recent study which showed functional P2X7R were expressed endogenously on eosinophils and that inhibition of the P2X7R, abrogated agonist (BzATP) induced IL-8 release from eosinophils [108].

Gene_expression (expressed) of P2X7R in eosinophils associated with agonist

7) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.09 Pain Relevance 0.32

These data indicate that PMN express functional P2X7R, but the cellular localisation of these receptors in this cell type remains unclear.

Gene_expression (express) of P2X7R

8) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.02 Pain Relevance 0.06

In particular, the P2X7 receptor (P2X7R) which is expressed primarily (though not exclusively) on cells of haemopoietic origin [3] is thought to play an important role in macrophage/microglial and granulocyte function by regulating cytokine production and apoptosis.

Neg (not) Gene_expression (expressed) of P2X7R in granulocyte associated with apoptosis and cytokine

9) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.40 Pain Relevance 0.47

It appears that microglia, the principal immune cells of the central nervous system, have enhanced P2X7R expression following inflammatory insults (see above) [3,75].

Gene_expression (expression) of P2X7R in central nervous system associated with inflammation and central nervous system

10) Confidence 0.77 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.51 Pain Relevance 0.30

We will focus on results obtained from studies of endogenous P2X7R in monocytes and macrophage and of heterologously expressed P2X7R in mammalian cells because few, if any, differences have been found when comparing data obtained from these systems.

Gene_expression (expressed) of P2X7R in macrophage

11) Confidence 0.72 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0.37 Pain Relevance 0.33

as well as enhances the expression and activity of P2X7R and panx1.

Gene_expression (expression) of P2X7R

12) Confidence 0.72 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0.05 Pain Relevance 0

Initial current is outward because NMDG+ initially is impermeable and only intracellular sodium passes outward but with time current turns inward due to NMDG+ entering the cell. b Example of reversal potential measurement experiments carried out at 2-s intervals during application of BzATP as shown in (a); reversal potential shifts to positive values which shows that NMDG+ is entering the cell. c, d Examples of the same experiment but from cell expressing mutated P2X7R; now there is no NMDG+ shift indicating no entry of NMDG+ into the cell, but the same mutated receptor shows enhanced dye uptake (e).

Gene_expression (expressing) of P2X7R

13) Confidence 0.72 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0 Pain Relevance 0.03

Fig. 2Two phases to P2X7R-mediated dye uptake revealed by inhibition of panx1. a Original traces of typical dye uptake experiments carried out on HEK 293 cells expressing rat P2X7R; each trace shows average ± SEM from 20 to 30 cells; control fluorescence (in arbitrary fluorescence units) saturates the optical system in both examples.

Gene_expression (expressing) of P2X7R

14) Confidence 0.72 Published 2009 Journal Purinergic Signal Section Body Doc Link PMC2686830 Disease Relevance 0 Pain Relevance 0

The substance P receptor is highly expressed in areas of the brain that are implicated in these behaviours, but also in other areas such as the nucleus accumbens which mediate the motivational properties of both natural rewards such as food and of drugs of abuse such as opiates.

Gene_expression (expressed) of P receptor in nucleus accumbens associated with nucleus accumbens, opiate and substance p

15) Confidence 0.68 Published 2000 Journal Nature Section Abstract Doc Link 10821273 Disease Relevance 0.35 Pain Relevance 0.76

Under these conditions, P2X7R activation results in a series of very rapid and reversible effects, including calcium-dependent translocation of plasma membrane phosphatidylserine, loss of mitochondrial membrane potential (without cytochrome c release), disruption of the actin filament/microtubule network and membrane blebbing.

Gene_expression (activation) of P2X7R in plasma

16) Confidence 0.66 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.73 Pain Relevance 0.03

Since the P2X7R is important in the production of both TNF-?

Gene_expression (important) of P2X7R

17) Confidence 0.66 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.96 Pain Relevance 0.44

Importantly, recent studies indicate that P2X7R activation may modulate a number of cell death processes through effects upon these key regulators of apoptosis.

Gene_expression (activation) of P2X7R associated with apoptosis and death

18) Confidence 0.66 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.52 Pain Relevance 0.15

Therapies directed at influencing the P2X7R

Gene_expression (influencing) of P2X7R

19) Confidence 0.66 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 1.15 Pain Relevance 0.45

This effect was not seen in P2X7R-deficient mice, indicating a P2X7R-mediated induction of cell death in these cells [34].

Gene_expression (induction) of P2X7R-mediated associated with death

20) Confidence 0.66 Published 2007 Journal J Inflamm (Lond) Section Body Doc Link PMC1838907 Disease Relevance 0.79 Pain Relevance 0.04

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