P2X4 | P2X receptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

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P2X4

  Target has curated data in GtoImmuPdb

Target id: 481

Nomenclature: P2X4

Family: P2X receptors

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 388 12q24.32 P2RX4 purinergic receptor P2X 4 5
Mouse 2 388 5 F P2rx4 purinergic receptor P2X, ligand-gated ion channel 4 13
Rat 2 388 12q16 P2rx4 purinergic receptor P2X 4 1-2,11-13,15
Previous and Unofficial Names
P2X purinoceptor 4 | purinergic receptor P2X, ligand-gated ion channel, 4 | purinergic receptor P2X, ligand gated ion channel, 4 | purinergic receptor P2X
Database Links
CATH/Gene3D 2.60.490.10
ChEMBL Target CHEMBL2104 (Hs), CHEMBL2176849 (Mm), CHEMBL2818 (Rn)
Ensembl Gene ENSG00000135124 (Hs), ENSMUSG00000029470 (Mm), ENSRNOG00000001300 (Rn)
Entrez Gene 5025 (Hs), 18438 (Mm), 29659 (Rn)
Human Protein Atlas ENSG00000135124 (Hs)
KEGG Gene hsa:5025 (Hs), mmu:18438 (Mm), rno:29659 (Rn)
OMIM 600846 (Hs)
RefSeq Nucleotide NM_002560 (Hs), NM_011026 (Mm), NM_031594 (Rn)
RefSeq Protein NP_002551 (Hs), NP_035156 (Mm), NP_113782 (Rn)
UniProtKB Q99571 (Hs), Q9JJX6 (Mm), P51577 (Rn)
Wikipedia P2RX4 (Hs)
Natural/Endogenous Ligands
ATP

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ATP Hs Agonist 6.3 pEC50 6
⤷ pEC50 6.3 (EC50 5x10-7 M) [6]
ATP Mm Agonist 6.0 pEC50 6
⤷ pEC50 6.0 (EC50 1x10-6 M) [6]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
paroxetine Hs Antagonist 5.0 – 6.0 pIC50 7,9
⤷ pIC50 5.0 – 6.0 [7,9]
5-BDBD Hs Antagonist 5.0 – 6.0 pIC50 7,9
⤷ pIC50 5.0 – 6.0 [7,9]
PSB-12062 Hs Antagonist 5.0 – 6.0 pIC50 7,9
⤷ pIC50 5.0 – 6.0 [7,9]
BX-430 Hs Antagonist 5.0 – 6.0 pIC50 7,9
⤷ pIC50 5.0 – 6.0 [7,9]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
ivermectin Rn Positive ~6.6 pEC50 - no 8
⤷ pEC50 ~6.6 (EC50 ~2.5x10-7 M) [8]
Not voltage dependent
Immunopharmacology Comments
P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [3-4].
Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  Human B cells express all P2 receptor subtypes.
References:  10
Immuno Cell Type:  T cells
Comment:  T cells express P2X receptors 1, 4 and 5. ATP-induced activation of these receptors in T cells is associated with proliferation, cytokine production and thymocyte apoptosis.
References:  4,14
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:1904124 microglial cell migration TAS
GO:1904141 positive regulation of microglial cell migration ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:1904141 positive regulation of microglial cell migration ISS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:1904124 microglial cell migration TAS
GO:1904141 positive regulation of microglial cell migration ISS

References

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1. Bo X, Zhang Y, Nassar M, Burnstock G, Schoepfer R. (1995) A P2X purinoceptor cDNA conferring a novel pharmacological profile. FEBS Lett., 375 (1-2): 129-33. [PMID:7498461]

2. Buell G, Lewis C, Collo G, North RA, Surprenant A. (1996) An antagonist-insensitive P2X receptor expressed in epithelia and brain. EMBO J., 15 (1): 55-62. [PMID:8598206]

3. Burnstock G, Boeynaems JM. (2014) Purinergic signalling and immune cells. Purinergic Signal., 10 (4): 529-64. [PMID:25352330]

4. Cekic C, Linden J. (2016) Purinergic regulation of the immune system. Nat. Rev. Immunol., 16 (3): 177-92. [PMID:26922909]

5. Garcia-Guzman M, Soto F, Gomez-Hernandez JM, Lund PE, Stühmer W. (1997) Characterization of recombinant human P2X4 receptor reveals pharmacological differences to the rat homologue. Mol. Pharmacol., 51 (1): 109-18. [PMID:9016352]

6. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J. Med. Chem., 45 (19): 4057-93. [PMID:12213051]

7. Jacobson KA, Müller CE. (2016) Medicinal chemistry of adenosine, P2Y and P2X receptors. Neuropharmacology, 104: 31-49. [PMID:26686393]

8. Khakh BS, Proctor WR, Dunwiddie TV, Labarca C, Lester HA. (1999) Allosteric control of gating and kinetics at P2X(4) receptor channels. J. Neurosci., 19 (17): 7289-99. [PMID:10460235]

9. North RA, Jarvis MF. (2013) P2X receptors as drug targets. Mol. Pharmacol., 83 (4): 759-69. [PMID:23253448]

10. Przybyła T, Sakowicz-Burkiewicz M, Pawełczyk T. (2018) Purinergic signaling in B cells. Acta Biochim. Pol., 65 (1): 1-7. [PMID:29360885]

11. Soto F, Garcia-Guzman M, Gomez-Hernandez JM, Hollmann M, Karschin C, Stühmer W. (1996) P2X4: an ATP-activated ionotropic receptor cloned from rat brain. Proc. Natl. Acad. Sci. U.S.A., 93 (8): 3684-8. [PMID:8622997]

12. Séguéla P, Haghighi A, Soghomonian JJ, Cooper E. (1996) A novel neuronal P2x ATP receptor ion channel with widespread distribution in the brain. J. Neurosci., 16 (2): 448-55. [PMID:8551329]

13. Townsend-Nicholson A, King BF, Wildman SS, Burnstock G. (1999) Molecular cloning, functional characterization and possible cooperativity between the murine P2X4 and P2X4a receptors. Brain Res. Mol. Brain Res., 64 (2): 246-54. [PMID:9931497]

14. Vaeth M, Feske S. (2018) Ion channelopathies of the immune system. Curr. Opin. Immunol., 52: 39-50. [PMID:29635109]

15. Wang CZ, Namba N, Gonoi T, Inagaki N, Seino S. (1996) Cloning and pharmacological characterization of a fourth P2X receptor subtype widely expressed in brain and peripheral tissues including various endocrine tissues. Biochem. Biophys. Res. Commun., 220 (1): 196-202. [PMID:8602843]

Contributors

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How to cite this page

Francesco Di Virgilio, Richard J. Evans, Simonetta Falzoni, Michael F. Jarvis, Charles Kennedy, Baljit S. Khakh, Brian King, Patrizia Pellegatti, John A. Peters.
P2X receptors: P2X4. Last modified on 13/09/2018. Accessed on 21/07/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=481.