Nomenclature: P2X3

Family: P2X receptors

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Contents

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
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
ATP
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
BzATP Hs Full agonist - -
αβ-meATP Hs Full agonist - -
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
TNP-ATP Hs Antagonist ~8.9 pIC50 40
pIC50 ~8.9 (IC50 ~1.3x10-9 M) [40]
AF353 Hs Antagonist ~8.0 pIC50 18
pIC50 ~8.0 (IC50 ~1x10-8 M) [18]
A317491 Hs Antagonist ~7.5 pIC50 23
pIC50 ~7.5 (IC50 ~3.1x10-8 M) [23]
RO3 Hs Antagonist ~7.5 pIC50 15
pIC50 ~7.5 (IC50 ~3.1x10-8 M) [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].
Tissue Distribution
Sensory nervous system - petrosal ganglia
Species:  Mouse
Technique:  mRNA, immunohistochemistry
References:  46
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
Parasympathetic ganglia - pelvic nerve
Species:  Mouse
Technique:  mRNA
References:  49
Sensory nervous system - trigeminal ganglia
Species:  Mouse
Technique:  mRNA, immunohistochemistry
References:  12,24,28,42
Enteric ganglia - Submucosal plexus
Species:  Rat
Technique:  Immunohistochemistry
References:  44
Parasympathetic ganglia - otic
Species:  Rat
Technique:  Immunohistochemistry
References:  29
Parasympathetic ganglia - sphenopalatine
Species:  Rat
Technique:  Immunohistochemistry
References:  29
Sensory nervous system - retinal ganglia
Species:  Rat
Technique:  mRNA, electrophysiology
References:  38
Sensory nervous system - carotid body
Species:  Rat
Technique:  Immunocytochemistry
References:  32
Nucleus Tractus Solitarius
Species:  Rat
Technique:  Electrophysiology, Immunohistochemistry
References:  28,41
Midbrain
Species:  Rat
Technique:  Electrophysiology
References:  13
Sympathetic ganglia - superior cervical
Species:  Rat
Technique:  Immunohistochemistry
References:  42
Sympathetic ganglia - celiac
Species:  Rat
Technique:  Immunohistochemistry
References:  42
Enteric ganglia - Intraganglionic laminar nerve
Species:  Rat
Technique:  Immunohistochemistry
References:  43
Cerebellum
Species:  Rat
Technique:  Electrophysiology
References:  19
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 - nodose ganglia
Species:  Rat
Technique:  mRNA, immunohistochemistry
References:  21,41
Sensory nervous system - petrosal ganglia
Species:  Rat
Technique:  mRNA, immunohistochemistry
References:  46
Sympathetic ganglia - superior cervical
Species:  Guinea pig
Technique:  Immunohistochemistry
References:  48
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
Enteric ganglia - Submucosal plexus
Species:  Guinea pig
Technique:  Immunohistochemistry
References:  31,39
Sensory nervous system - vagus nerve terminals
Species:  Dog
Technique:  Immunohistochemistry, electrophysiology
References:  25-26,30,34,45
Parasympathetic ganglia - submandibular
Species:  Cat
Technique:  Immunohistochemistry
References:  33
Sensory nervous system - carotid body
Species:  Cat
Technique:  Immunocytochemistry
References:  32
Parasympathetic ganglia - intramural
Species:  Cat
Technique:  Immunohistochemistry
References:  33
Physiological Consequences of Altering Gene Expression
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
Decreased ATP-evoked currents associated with decreased receptor expression
Species:  Rat
Tissue:  Dorsal root ganglia neurones
Technique:  Antisense/siRNA
References:  1,20
Reduced/no effect on inflammatory pain
Species:  Rat
Tissue:  whole animal work
Technique:  Gene knockout, Antisense/siRNA
References:  1,20,22-23,47
Decreased ATP-evoked currents
Species:  Mouse
Tissue:  Dorsal root ganglia neurones
Technique:  Gene knockout
References:  9-10,35-36
Reduced neuropathic pain
Species:  Rat
Tissue:  whole animal work
Technique:  Antisense/siRNA
References:  20,23
Hyporeflexia
Species:  Rat
Tissue:  Urinary (bladder)
Technique:  Antisense/siRNA
References:  15,17,47

REFERENCES

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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. Neuroreport10 (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]

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8. Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN. (1995) A P2X purinoceptor expressed by a subset of sensory neurons. Nature377 (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. Nature407 (6807): 1011-5. [PMID:11069181]

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12. Cook SP, Vulchanova L, Hargreaves KM, Elde R, McCleskey EW. (1997) Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature387 (6632): 505-8. [PMID:9168113]

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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]

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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. Pain99 (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. Neuroreport12 (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 Endod94 (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]

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29. Ma B, Ruan HZ, Burnstock G, Dunn PM. (2005) Differential expression of P2X receptors on neurons from different parasympathetic ganglia. Neuropharmacology48 (5): 766-77. [PMID:15814110]

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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. Neuropharmacology36 (9): 1229-42. [PMID:9364478]

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43. 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]

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

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 14/03/2014. Accessed on 24/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=480.

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