P2X4 | P2X receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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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

   GtoImmuPdb view: OFF :     P2X4 has curated data in GtoImmuPdb

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
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units 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
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units 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 Affinity Units 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


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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]


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How to cite this page

Francesco Di Virgilio, Richard J Evans, Simonetta Falzoni, Michael F Jarvis, Charles Kennedy, Brian King, John A. Peters, Baljit S. Khakh, Patrizia Pellegatti.
P2X receptors: P2X4. Last modified on 13/09/2018. Accessed on 11/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=481.