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P2X3

Family: P2X receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Antagonists
Tissue Distribution
Physiological Consequences of Altering Gene Expression
References
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 397 11q12 P2RX3 purinergic receptor P2X, ligand-gated ion channel, 3 16
Mouse 2 397 2 D P2rx3 purinergic receptor P2X, ligand-gated ion channel, 3 37
Rat 2 397 3q24 P2rx3 purinergic receptor P2X, ligand-gated ion channel, 3 8
Previous and Unofficial Names
P2X3
ATP receptor
P2X purinoceptor 3
purinergic receptor P2X ligand-gated ion channel, 3
purinergic receptor P2X, ligand-gated ion channel, 3
4930513E20Rik
Database Links
ChEMBL Target 11904 (Hs), 10275 (Rn)
Ensembl ENSG00000109991 (Hs), ENSMUSG00000027071 (Mm), ENSRNOG00000008552 (Rn)
Entrez Gene 5024 (Hs), 228139 (Mm), 81739 (Rn)
GeneCards P2RX3 (Hs)
GenitoUrinary Development Molecular Anatomy Project P2rx3 (Mm)
HomoloGene 1922 (Hs)
Human Protein Reference Database 09016 (Hs)
InterPro P56373 (Hs), Q3UR32 (Mm), P49654 (Rn)
KEGG Gene hsa:5024 (Hs), mmu:228139 (Mm), rno:81739 (Rn)
OMIM 600843 (Hs)
PharmGKB Gene PA32863 (Hs)
PhosphoSitePlus P56373 (Hs), Q3UR32 (Mm), P49654 (Rn)
Protein Ontology (PRO) PRO:000012190 (Hs)
RefSeq Nucleotide NM_002559 (Hs), NM_145526 (Mm), NM_031075 (Rn)
RefSeq Protein NP_002550 (Hs), NP_663501 (Mm), NP_112337 (Rn)
TreeFam ENSG00000109991 (Hs), ENSMUSG00000027071 (Mm), ENSRNOG00000008552 (Rn)
UniGene Hs. 146738 (Hs)
UniProt P56373 (Hs), Q3UR32 (Mm), P49654 (Rn)
Wikipedia P2X3
P2X receptors
Search for 3D structures on the PDB
Search by keyword: P2X receptors P2X3 Search by accession number: P49654, Q3UR32, P56373
Natural/Endogenous Ligand(s)
ATP
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Reference
TNP-ATP Hs 8.9

- 		pIC50

- 		40

AF353 Hs 8.0

- 		pIC50

- 		18

A317491 Hs 7.5

- 		pIC50

- 		23

RO3 Hs 7.5

- 		pIC50

- 		15

Antagonist Comments
A number of studies have demonstrated the effects of selective P2X3 antagonist treatment. These include blockade of ATP-evoked currents in mouse and rat [23] dorsal root ganglia neurones, as well as reduction of chemical-induced pain [22], inflammatory pain [23], and neuropathic pain [23] in rat. Hyporeflexia in the rat urinary bladder in response to antagonist treatment has also been demonstrated [15].

Explore drug-target interactions for this set of compounds using iPHACE

Tissue Distribution
Parasympathetic ganglia - pelvic nerve
Species:  Mouse
Technique:  mRNA
References:  49
Sensory nervous system - taste buds
Species:  Mouse
Technique:  Electrophysiology
References:  5,14
Sensory nervous system - dorsal root ganglia
Species:  Mouse
Technique:  mRNA, immunohistochemistry
References:  6,8,11,27
Sensory nervous system - trigeminal ganglia
Species:  Mouse
Technique:  mRNA, immunohistochemistry
References:  12,24,28,42
Sensory nervous system - petrosal ganglia
Species:  Mouse
Technique:  mRNA, immunohistochemistry
References:  46
Nucleus Tractus Solitarius
Species:  Rat
Technique:  Electrophysiology, Immunohistochemistry
References:  28,41
Cerebellum
Species:  Rat
Technique:  Electrophysiology
References:  19
Midbrain
Species:  Rat
Technique:  Electrophysiology
References:  13
Parasympathetic ganglia - sphenopalatine
Species:  Rat
Technique:  Immunohistochemistry
References:  29
Sensory nervous system - nodose ganglia
Species:  Rat
Technique:  mRNA, immunohistochemistry
References:  21,41
Sensory nervous system - petrosal ganglia
Species:  Rat
Technique:  mRNA, immunohistochemistry
References:  46
Sensory nervous system - dorsal root ganglia
Species:  Rat
Technique:  mRNA, immunohistochemistry
References:  6,8,11,27
Sensory nervous system - trigeminal ganglia
Species:  Rat
Technique:  mRNA, immunohistochemistry
References:  12,24,28,42
Sensory nervous system - carotid body
Species:  Rat
Technique:  Immunocytochemistry
References:  32
Sensory nervous system - retinal ganglia
Species:  Rat
Technique:  mRNA, electrophysiology
References:  38
Sympathetic ganglia - superior cervical
Species:  Rat
Technique:  Immunohistochemistry
References:  42
Sympathetic ganglia - celiac
Species:  Rat
Technique:  Immunohistochemistry
References:  42
Parasympathetic ganglia - otic
Species:  Rat
Technique:  Immunohistochemistry
References:  29
Enteric ganglia - Intraganglionic laminar nerve
Species:  Rat
Technique:  Immunohistochemistry
References:  44
Enteric ganglia - Submucosal plexus
Species:  Rat
Technique:  Immunohistochemistry
References:  43
Sympathetic ganglia - superior cervical
Species:  Guinea pig
Technique:  Immunohistochemistry
References:  48
Enteric ganglia - Submucosal plexus
Species:  Guinea pig
Technique:  Immunohistochemistry
References:  31,39
Parasympathetic ganglia - pelvic nerve
Species:  Guinea pig
Technique:  mRNA
References:  49
Enteric ganglia - Myenteric plexus (AH-type)
Species:  Guinea pig
Technique:  Electrophysiology
References:  2-4,7
Sensory nervous system - vagus nerve terminals
Species:  Dog
Technique:  Immunohistochemistry, electrophysiology
References:  25-26,30,34,45
Parasympathetic ganglia - intramural
Species:  Cat
Technique:  Immunohistochemistry
References:  33
Sensory nervous system - carotid body
Species:  Cat
Technique:  Immunocytochemistry
References:  32
Parasympathetic ganglia - submandibular
Species:  Cat
Technique:  Immunohistochemistry
References:  33
Physiological Consequences of Altering Gene Expression
Reduced neuropathic pain
Species:  Rat
Tissue:  whole animal work
Technique:  Antisense/siRNA
References:  20,23
Decreased ATP-evoked currents
Species:  Mouse
Tissue:  Dorsal root ganglia neurones
Technique:  Gene knockout
References:  9-10,35-36
Reduced neurogenic pain
Species:  Mouse
Tissue:  whole animal work
Technique:  Gene knockout
References:  10,35-36
Reduced chemical pain
Species:  Rat
Tissue:  whole animal work
Technique:  Antisense/siRNA
References:  1,20,23
Reduced/no effect on inflammatory pain
Species:  Rat
Tissue:  whole animal work
Technique:  Gene knockout, Antisense/siRNA
References:  1,20,22-23,47
Hyporeflexia
Species:  Rat
Tissue:  Urinary (bladder)
Technique:  Antisense/siRNA
References:  15,17,47
Decreased ATP-evoked currents associated with decreased receptor expression
Species:  Rat
Tissue:  Dorsal root ganglia neurones
Technique:  Antisense/siRNA
References:  1,20

REFERENCES

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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. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. 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]

17. Gever, JR; Cockayne, DA; Dillon, MP; Burnstock, G; Ford, AP. (2006) Pharmacology of P2X channels. Pflugers Arch., 452 (5): 513-37. [PMID:16649055]

18. 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]

19. 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]

20. 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]

21. 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]

22. 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]

23. 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. U.S.A., 99 (26): 17179-84. [PMID:12482951]

24. 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]

25. 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]

26. 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]

27. 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]

28. Llewellyn-Smith, IJ; Burnstock, G. (1998) Ultrastructural localization of P2X3 receptors in rat sensory neurons. Neuroreport, 9 (11): 2545-50. [PMID:9721930]

29. 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]

30. 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]

31. 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]

32. 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]

33. 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]

34. 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]

35. 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]

36. 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]

37. 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]

38. 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]

39. 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]

40. 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]

41. 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]

42. 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]

43. Xiang, Z; Burnstock, G. (2004) P2X2 and P2X3 purinoceptors in the rat enteric nervous system. Histochem. Cell Biol., 121 (3): 169-79. [PMID:14767775]

44. 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]

45. 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]

46. 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]

47. 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]

48. 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]

49. 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]

To cite this database page, please use the following:

Francesco Di Virgilio, Richard J Evans, Michael F Jarvis, Charles Kennedy, Baljit S. Khakh, Patrizia Pellegatti, John A. Peters.
P2X receptors: P2X3. Last modified on 08/03/2013. Accessed on 25/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=480.


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