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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 2 | 397 | 11q12.1 | P2RX3 | purinergic receptor P2X 3 | 20 |
| Mouse | 2 | 397 | 2 D | P2rx3 | purinergic receptor P2X, ligand-gated ion channel, 3 | 45 |
| Rat | 2 | 397 | 3q24 | P2rx3 | purinergic receptor P2X 3 | 10 |
| Previous and Unofficial Names |
| P2X purinoceptor 3 | purinergic receptor P2X, ligand gated ion channel, 3 | purinergic receptor P2X |
| Database Links |
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| Alphafold | P56373 (Hs), Q3UR32 (Mm), P49654 (Rn) |
| CATH/Gene3D | 2.60.490.10 |
| ChEMBL Target | CHEMBL2998 (Hs), CHEMBL2401608 (Mm), CHEMBL4824 (Rn) |
| Ensembl Gene | ENSG00000109991 (Hs), ENSMUSG00000027071 (Mm), ENSRNOG00000008552 (Rn) |
| Entrez Gene | 5024 (Hs), 228139 (Mm), 81739 (Rn) |
| Human Protein Atlas | ENSG00000109991 (Hs) |
| KEGG Gene | hsa:5024 (Hs), mmu:228139 (Mm), rno:81739 (Rn) |
| OMIM | 600843 (Hs) |
| Pharos | P56373 (Hs) |
| RefSeq Nucleotide | NM_002559 (Hs), NM_145526 (Mm), NM_031075 (Rn) |
| RefSeq Protein | NP_002550 (Hs), NP_663501 (Mm), NP_112337 (Rn) |
| UniProtKB | P56373 (Hs), Q3UR32 (Mm), P49654 (Rn) |
| Wikipedia | P2RX3 (Hs) |
| Natural/Endogenous Ligands |
| ATP |
Download all structure-activity data for this target as a CSV file 
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| A number of studies have demonstrated the effects of selective P2X3 antagonist treatment. These include blockade of ATP-evoked currents in mouse and rat [29] dorsal root ganglia neurones, as well as reduction of chemical-induced pain [26], inflammatory pain [29], and neuropathic pain [29] in rat. Hyporeflexia in the rat urinary bladder in response to antagonist treatment has also been demonstrated [18]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 [8-9]. |
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1. Barclay J, Patel S, Dorn G, Wotherspoon G, Moffatt S, Eunson L, Abdel'al S, Natt F, Hall J, Winter J et al.. (2002) Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain. J Neurosci, 22 (18): 8139-47. [PMID:12223568]
2. Benkó R, Undi S, Wolf M, Barthó L. (2005) Effects of acute administration of and tachyphylaxis to alpha,beta-methylene ATP in the guinea-pig small intestine. Basic Clin Pharmacol Toxicol, 97 (6): 369-73. [PMID:16364052]
3. Bertrand PP, Bornstein JC. (2002) ATP as a putative sensory mediator: activation of intrinsic sensory neurons of the myenteric plexus via P2X receptors. J Neurosci, 22 (12): 4767-75. [PMID:12077173]
4. Bian X, Ren J, DeVries M, Schnegelsberg B, Cockayne DA, Ford AP, Galligan JJ. (2003) Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit. J Physiol (Lond.), 551 (Pt 1): 309-22. [PMID:12813150]
5. Bo X, Alavi A, Xiang Z, Oglesby I, Ford A, Burnstock G. (1999) Localization of ATP-gated P2X2 and P2X3 receptor immunoreactive nerves in rat taste buds. Neuroreport, 10 (5): 1107-11. [PMID:10321492]
6. Bradbury EJ, Burnstock G, McMahon SB. (1998) The expression of P2X3 purinoreceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor. Mol Cell Neurosci, 12 (4-5): 256-68. [PMID:9828090]
7. Burnstock G. (2001) Purine-mediated signalling in pain and visceral perception. Trends Pharmacol Sci, 22 (4): 182-8. [PMID:11282418]
8. Burnstock G, Boeynaems JM. (2014) Purinergic signalling and immune cells. Purinergic Signal, 10 (4): 529-64. [PMID:25352330]
9. Cekic C, Linden J. (2016) Purinergic regulation of the immune system. Nat Rev Immunol, 16 (3): 177-92. [PMID:26922909]
10. Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN. (1995) A P2X purinoceptor expressed by a subset of sensory neurons. Nature, 377 (6548): 428-31. [PMID:7566119]
11. Cockayne DA, Dunn PM, Zhong Y, Rong W, Hamilton SG, Knight GE, Ruan HZ, Ma B, Yip P, Nunn P, McMahon SB, Burnstock G, Ford AP. (2005) P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol (Lond.), 567 (Pt 2): 621-39. [PMID:15961431]
12. Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L et al.. (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature, 407 (6807): 1011-5. [PMID:11069181]
13. Collo G, North RA, Kawashima E, Merlo-Pich E, Neidhart S, Surprenant A, Buell G. (1996) Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. J Neurosci, 16 (8): 2495-507. [PMID:8786426]
14. Cook SP, Vulchanova L, Hargreaves KM, Elde R, McCleskey EW. (1997) Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature, 387 (6632): 505-8. [PMID:9168113]
15. Davenport AJ, Neagoe I, Bräuer N, Koch M, Rotgeri A, Nagel J, Laux-Biehlmann A, Machet F, Coelho AM, Boyce S et al.. (2021) Eliapixant is a selective P2X3 receptor antagonist for the treatment of disorders associated with hypersensitive nerve fibers. Sci Rep, 11 (1): 19877. [PMID:34615939]
16. Díaz-Hernández M, Pintor J, Castro E, Miras-Portugal MT. (2002) Co-localisation of functional nicotinic and ionotropic nucleotide receptors in isolated cholinergic synaptic terminals. Neuropharmacology, 42 (1): 20-33. [PMID:11750913]
17. Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L, Hellekant G, Kinnamon SC. (2005) ATP signaling is crucial for communication from taste buds to gustatory nerves. Science, 310 (5753): 1495-9. [PMID:16322458]
18. Ford AP, Gever JR, Nunn PA, Zhong Y, Cefalu JS, Dillon MP, Cockayne DA. (2006) Purinoceptors as therapeutic targets for lower urinary tract dysfunction. Br J Pharmacol, 147 Suppl 2: S132-43. [PMID:16465177]
19. Garceau D, Chauret N. (2019) BLU-5937: A selective P2X3 antagonist with potent anti-tussive effect and no taste alteration. Pulm Pharmacol Ther, 56: 56-62. [PMID:30902655]
20. Garcia-Guzman M, Stühmer W, Soto F. (1997) Molecular characterization and pharmacological properties of the human P2X3 purinoceptor. Brain Res Mol Brain Res, 47 (1-2): 59-66. [PMID:9221902]
21. Gever JR, Cockayne DA, Dillon MP, Burnstock G, Ford AP. (2006) Pharmacology of P2X channels. Pflugers Arch, 452 (5): 513-37. [PMID:16649055]
22. Gever JR, Soto R, Henningsen RA, Martin RS, Hackos DH, Panicker S, Rubas W, Oglesby IB, Dillon MP, Milla ME et al.. (2010) AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist. Br J Pharmacol, 160 (6): 1387-98. [PMID:20590629]
23. Hervás C, Pérez-Sen R, Miras-Portugal MT. (2005) Presence of diverse functional P2X receptors in rat cerebellar synaptic terminals. Biochem Pharmacol, 70 (5): 770-85. [PMID:16018975]
24. Honore P, Kage K, Mikusa J, Watt AT, Johnston JF, Wyatt JR, Faltynek CR, Jarvis MF, Lynch K. (2002) Analgesic profile of intrathecal P2X(3) antisense oligonucleotide treatment in chronic inflammatory and neuropathic pain states in rats. Pain, 99 (1-2): 11-9. [PMID:12237180]
25. Hubscher CH, Petruska JC, Rau KK, Johnson RD. (2001) Co-expression of P2X receptor subunits on rat nodose neurons that bind the isolectin GS-I-B4. Neuroreport, 12 (13): 2995-7. [PMID:11588618]
26. Ito K, Iwami A, Katsura H, Ikeda M. (2008) Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol, 377 (4-6): 483-90. [PMID:17917716]
27. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J Med Chem, 45 (19): 4057-93. [PMID:12213051]
28. Jacobson KA, Müller CE. (2016) Medicinal chemistry of adenosine, P2Y and P2X receptors. Neuropharmacology, 104: 31-49. [PMID:26686393]
29. Jarvis MF, Burgard EC, McGaraughty S, Honore P, Lynch K, Brennan TJ, Subieta A, Van Biesen T, Cartmell J, Bianchi B et al.. (2002) A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci USA, 99 (26): 17179-84. [PMID:12482951]
30. Jiang J, Gu J. (2002) Expression of adenosine triphosphate P2X3 receptors in rat molar pulp and trigeminal ganglia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 94 (5): 622-6. [PMID:12424458]
31. Kai H, Horiguchi T, Kameyma T, Onodera N, Itoh N, Fujii Y, Ichihashi Y, Hirai K, Shintani T, Nakamura K et al.. (2021) Discovery of clinical candidate Sivopixant (S-600918): Lead optimization of dioxotriazine derivatives as selective P2X3 receptor antagonists. Bioorg Med Chem Lett, 52: 128384. [PMID:34587541]
32. Kamei J, Takahashi Y. (2006) Involvement of ionotropic purinergic receptors in the histamine-induced enhancement of the cough reflex sensitivity in guinea pigs. Eur J Pharmacol, 547 (1-3): 160-4. [PMID:16935279]
33. Kamei J, Takahashi Y, Yoshikawa Y, Saitoh A. (2005) Involvement of P2X receptor subtypes in ATP-induced enhancement of the cough reflex sensitivity. Eur J Pharmacol, 528 (1-3): 158-61. [PMID:16321375]
34. Lewis C, Neidhart S, Holy C, North RA, Buell G, Surprenant A. (1995) Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature, 377 (6548): 432-5. [PMID:7566120]
35. Llewellyn-Smith IJ, Burnstock G. (1998) Ultrastructural localization of P2X3 receptors in rat sensory neurons. Neuroreport, 9 (11): 2545-50. [PMID:9721930]
36. Ma B, Ruan HZ, Burnstock G, Dunn PM. (2005) Differential expression of P2X receptors on neurons from different parasympathetic ganglia. Neuropharmacology, 48 (5): 766-77. [PMID:15814110]
37. Pelleg A, Hurt CM. (1996) Mechanism of action of ATP on canine pulmonary vagal C fibre nerve terminals. J Physiol (Lond.), 490 ( Pt 1): 265-75. [PMID:8745294]
38. Poole DP, Castelucci P, Robbins HL, Chiocchetti R, Furness JB. (2002) The distribution of P2X3 purine receptor subunits in the guinea pig enteric nervous system. Auton Neurosci, 101 (1-2): 39-47. [PMID:12462358]
39. Prasad M, Fearon IM, Zhang M, Laing M, Vollmer C, Nurse CA. (2001) Expression of P2X2 and P2X3 receptor subunits in rat carotid body afferent neurones: role in chemosensory signalling. J Physiol (Lond.), 537 (Pt 3): 667-77. [PMID:11744746]
40. Przybyła T, Sakowicz-Burkiewicz M, Pawełczyk T. (2018) Purinergic signaling in B cells. Acta Biochim Pol, 65 (1): 1-7. [PMID:29360885]
41. Ruan HZ, Birder LA, Xiang Z, Chopra B, Buffington T, Tai C, Roppolo JR, de Groat WC, Burnstock G. (2006) Expression of P2X and P2Y receptors in the intramural parasympathetic ganglia of the cat urinary bladder. Am J Physiol Renal Physiol, 290 (5): F1143-52. [PMID:16332929]
42. Ruan T, Lin YS, Lin KS, Kou YR. (2006) Mediator mechanisms involved in TRPV1 and P2X receptor-mediated, ROS-evoked bradypneic reflex in anesthetized rats. J Appl Physiol, 101 (2): 644-54. [PMID:16627682]
43. Shimizu I, Iida T, Guan Y, Zhao C, Raja SN, Jarvis MF, Cockayne DA, Caterina MJ. (2005) Enhanced thermal avoidance in mice lacking the ATP receptor P2X3. Pain, 116 (1-2): 96-108. [PMID:15927378]
44. Souslova V, Cesare P, Ding Y, Akopian AN, Stanfa L, Suzuki R, Carpenter K, Dickenson A, Boyce S, Hill R et al.. (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature, 407 (6807): 1015-7. [PMID:11069182]
45. Souslova V, Ravenall S, Fox M, Wells D, Wood JN, Akopian AN. (1997) Structure and chromosomal mapping of the mouse P2X3 gene. Gene, 195 (1): 101-11. [PMID:9300827]
46. Taschenberger H, Jüttner R, Grantyn R. (1999) Ca2+-permeable P2X receptor channels in cultured rat retinal ganglion cells. J Neurosci, 19 (9): 3353-66. [PMID:10212295]
47. Vaeth M, Feske S. (2018) Ion channelopathies of the immune system. Curr Opin Immunol, 52: 39-50. [PMID:29635109]
48. Van Nassauw L, Brouns I, Adriaensen D, Burnstock G, Timmermans JP. (2002) Neurochemical identification of enteric neurons expressing P2X(3) receptors in the guinea-pig ileum. Histochem Cell Biol, 118 (3): 193-203. [PMID:12271355]
49. Virginio C, Robertson G, Surprenant A, North RA. (1998) Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X1, P2X3, and heteromeric P2X2/3 receptors. Mol Pharmacol, 53 (6): 969-73. [PMID:9614197]
50. Vulchanova L, Riedl MS, Shuster SJ, Buell G, Surprenant A, North RA, Elde R. (1997) Immunohistochemical study of the P2X2 and P2X3 receptor subunits in rat and monkey sensory neurons and their central terminals. Neuropharmacology, 36 (9): 1229-42. [PMID:9364478]
51. Xiang Z, Bo X, Burnstock G. (1998) Localization of ATP-gated P2X receptor immunoreactivity in rat sensory and sympathetic ganglia. Neurosci Lett, 256 (2): 105-8. [PMID:9853714]
52. Xiang Z, Burnstock G. (2004) Development of nerves expressing P2X3 receptors in the myenteric plexus of rat stomach. Histochem Cell Biol, 122 (2): 111-9. [PMID:15258768]
53. Xiang Z, Burnstock G. (2004) P2X2 and P2X3 purinoceptors in the rat enteric nervous system. Histochem Cell Biol, 121 (3): 169-79. [PMID:14767775]
54. Xu J, Kussmaul W, Kurnik PB, Al-Ahdav M, Pelleg A. (2005) Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. V. Role of purinergic receptors. Am J Physiol Regul Integr Comp Physiol, 288 (3): R651-5. [PMID:15539614]
55. Zhang M, Zhong H, Vollmer C, Nurse CA. (2000) Co-release of ATP and ACh mediates hypoxic signalling at rat carotid body chemoreceptors. J Physiol (Lond.), 525 Pt 1: 143-58. [PMID:10811733]
56. Zhong Y, Dunn PM, Bardini M, Ford AP, Cockayne DA, Burnstock G. (2001) Changes in P2X receptor responses of sensory neurons from P2X3-deficient mice. Eur J Neurosci, 14 (11): 1784-92. [PMID:11860473]
57. Zhong Y, Dunn PM, Burnstock G. (2000) Guinea-pig sympathetic neurons express varying proportions of two distinct P2X receptors. J Physiol (Lond.), 523 Pt 2: 391-402. [PMID:10699083]
58. Zhong Y, Dunn PM, Burnstock G. (2001) Multiple P2X receptors on guinea-pig pelvic ganglion neurons exhibit novel pharmacological properties. Br J Pharmacol, 132 (1): 221-33. [PMID:11156581]
target has curated data in GtoImmuPdb
