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P2X1

Family: P2X receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Antagonists
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Gene Expression and Pathophysiology
Biologically Significant Variants
General Comments
References
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 399 17p13.3 P2RX1 purinergic receptor P2X, ligand-gated ion channel, 1 36
Mouse 2 399 11 B4 P2rx1 purinergic receptor P2X, ligand-gated ion channel, 1 20
Rat 2 399 10q24 P2rx1 purinergic receptor P2X, ligand-gated ion channel, 1 35
Previous and Unofficial Names
P2XR1
P2X1
P2XMR
ATP receptor
P2X purinoceptor 1
RP-2 protein
purinergic receptor P2X, ligand-gated ion channel, 1
RP-2
P2x
P2X1 receptor
Pdcd3
AI323649
BB122383
Database Links
ChEMBL Target 10535 (Hs), 100870 (Mm), 10536 (Rn)
Ensembl ENSG00000108405 (Hs), ENSMUSG00000020787 (Mm), ENSRNOG00000017606 (Rn)
Entrez Gene 5023 (Hs), 18436 (Mm), 25505 (Rn)
GeneCards P2RX1 (Hs)
GenitoUrinary Development Molecular Anatomy Project P2rx1 (Mm)
HomoloGene 1921 (Hs)
Human Protein Reference Database 07526 (Hs)
InterPro P51575 (Hs), P51576 (Mm), P47824 (Rn)
KEGG Gene hsa:5023 (Hs), mmu:18436 (Mm), rno:25505 (Rn)
OMIM 600845 (Hs)
PharmGKB Gene PA32861 (Hs)
PhosphoSitePlus P51575 (Hs), P51576 (Mm)
Protein Ontology (PRO) PRO:000012188 (Hs)
RefSeq Nucleotide NM_002558 (Hs), NM_008771 (Mm), NM_012997 (Rn), AF231010 (Rn)
RefSeq Protein NP_002549 (Hs), NP_032797 (Mm), NP_037129 (Rn), Q9JIF8 (Rn)
TreeFam ENSG00000108405 (Hs), ENSMUSG00000020787 (Mm), ENSRNOG00000017606 (Rn)
UniGene Hs. 41735 (Hs)
UniProt P51575 (Hs), P51576 (Mm), P47824 (Rn)
Wikipedia P2X1
P2X receptors
Search for 3D structures on the PDB
Search by keyword: P2X receptors P2X1 Search by accession number: P51575, P47824, P51576
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

- 		42

NF449 Hs 6.3

- 		pIC50

- 		14

Tissue Distribution
Smooth muscle; bladder, vas deferens, arteries
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, Northern blot, RT-PCR, Western Blot
References:  2,4,21,36,45
blood cells; platelets, mast cells, lymphocytes
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, western blotting
References:  30,33,40,46
Heart tissue.
Expression level:  Medium
Species:  Human
Technique:  Immunohistochemistry, Western blotting, RT-PCR
References:  3,11,13
Macrophages, neutrophils, megakaryocytes/platelts, pancreatic beta cells
Expression level:  Medium
Species:  Mouse
Technique:  immunohistochemistry, knockouts
References:  18,31-32,41
Smooth muscle; vas deferens, bladder, arteries
Expression level:  High
Species:  Mouse
Technique:  immunohistochemistry
References:  23,37-39
Astrocytes, cerebellar granule neurons
Expression level:  Medium
Species:  Mouse
Technique:  RT-PCR
References:  16,34
Spinal cord, superior cervical ganalion, sensory ganglia, hippocampal neurons
Expression level:  Medium
Species:  Rat
Technique:  In situ hybridization, RT-PCR
References:  5-6,15,19,22,24,29
Smooth muscle; vas deferens, bladder, arteries, portal vein, myometrium
Expression level:  High
Species:  Rat
Technique:  Immunohistochemistry and in situ hybridisation.
References:  5-6,15,19,22,24,35,43
Tissue Distribution Comments
The commonly used anti-P2X1 receptor antibody may not be selective in neuronal tissues [1] and so studies using this approach have not been included.
Physiological Consequences of Altering Gene Expression
Reduced kidney autoregulation of blood flow
Species:  Mouse
Tissue:  Kidney arterioles
Technique:  knock out
References:  12
Decreased mortality in thromboembolism models
Species:  Mouse
Tissue:  Platelets
Technique:  Knock out
References:  7,10
Increased mortality in thromboembolism models
Species:  Mouse
Tissue:  Platelets
Technique:  megakaryocyte specific over-expression
References:  27
Reduced ATP evoked P2X receptor currents in macrophages
Species:  Mouse
Tissue:  Macrophages
Technique:  Knock out
References:  32
Male infertility
Species:  Mouse
Tissue:  Vas deferens
Technique:  Knock out
References:  23
Reduced nerve evoked bladder contraction
Species:  Mouse
Tissue:  Urinary (bladder)
Technique:  Knock out
References:  37
Reduced nerve evoked artery contraction
Species:  Mouse
Tissue:  Mesenteric artery
Technique:  knock out
References:  17,39
Physiological Consequences of Altering Gene Expression Comments
P2X1 receptor knockout mice also reveal a role for the receptors in neutrophil chemotaxis [18]
Gene Expression and Pathophysiology
Upregulation
Tissue or cell type:  Heart
Pathophysiology:  Congestive heart failure
Species:  Human
Technique:  RT-PCR
References:  11
Upregulation
Tissue or cell type:  Heart-atria
Pathophysiology:  Dilated cardiomyopathy
Species:  Human
Technique:  Western blot
References:  3
Downregulation
Tissue or cell type:  Shear stress
Pathophysiology:  Umbilical vein smooth muscle
Species:  Human
Technique:  RT-PCR, Western blot, immunohistochemistry
References:  44
Upregulation
Tissue or cell type:  Urinary-bladder
Pathophysiology:  Outlet obstruction
Species:  Human
Technique:  RT-PCR
References:  25
Biologically Significant Variants
P2X1a receptor isoform ( (deletion:175-201)
Nucleotide accession:  AF231010 
Protein accession:  Q9JIF8 
Amino acids:  372
Type:  Splice variant.
Species:  Rat
References:  26
P2X1del (deletion:346-379)
Type:  Splice variant.
Species:  Human
References:  9
P2X1del (deletion:176-192)
Type:  Splice variant
Species:  Human
References:  8
P2X1delL (deletion:353)
Type:  Splice variant.
Species:  Human
References:  28
General Comments
An alternatively spliced variant of the rat P2X1 subunit, provisionally termed p2X1a which lacks function as a homomer has been described [26]. An inactive, naturally occurring human mutant dominant negative P2X receptor has also been reported [28].

REFERENCES

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1. Ashour, F; Atterbury-Thomas, M; Deuchars, J; Evans, RJ. (2006) An evaluation of antibody detection of the P2X1 receptor subunit in the CNS of wild type and P2X1-knockout mice. Neurosci. Lett., 397 (1-2): 120-5. [PMID:16384637]

2. Banks, FC; Knight, GE; Calvert, RC; Thompson, CS; Morgan, RJ; Burnstock, G. (2006) The purinergic component of human vas deferens contraction. Fertil. Steril., 85 (4): 932-9. [PMID:16580377]

3. Berry, DA; Barden, JA; Balcar, VJ; Keogh, A; dos Remedios, CG. (1999) Increase in expression of P2X1 receptors in the atria of patients suffering from dilated cardiomyopathy. Electrophoresis, 20 (10): 2059-64. [PMID:10451115]

4. Bo, X; Karoon, P; Nori, SL; Bardini, M; Burnstock, G. (1998) P2X purinoceptors in postmortem human cerebral arteries. J. Cardiovasc. Pharmacol., 31 (5): 794-9. [PMID:9593081]

5. Chan, CM; Unwin, RJ; Bardini, M; Oglesby, IB; Ford, AP; Townsend-Nicholson, A; Burnstock, G. (1998) Localization of P2X1 purinoceptors by autoradiography and immunohistochemistry in rat kidneys. Am. J. Physiol., 274 (4 Pt 2): F799-804. [PMID:9575906]

6. 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]

7. Erhardt, JA; Toomey, JR; Douglas, SA; Johns, DG. (2006) P2X1 stimulation promotes thrombin receptor-mediated platelet aggregation. J. Thromb. Haemost., 4 (4): 882-90. [PMID:16634759]

8. Greco, NJ; Tonon, G; Chen, W; Luo, X; Dalal, R; Jamieson, GA. (2001) Novel structurally altered P(2X1) receptor is preferentially activated by adenosine diphosphate in platelets and megakaryocytic cells. Blood, 98 (1): 100-7. [PMID:11418468]

9. Hardy, LA; Harvey, IJ; Chambers, P; Gillespie, JI. (2000) A putative alternatively spliced variant of the P2X(1) purinoreceptor in human bladder. Exp. Physiol., 85 (4): 461-3. [PMID:10918085]

10. Hechler, B; Lenain, N; Marchese, P; Vial, C; Heim, V; Freund, M; Cazenave, JP; Cattaneo, M; Ruggeri, ZM; Evans, R; et al.. (2003) A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo. J. Exp. Med., 198 (4): 661-7. [PMID:12913094]

11. Hou, M; Malmsjö, M; Möller, S; Pantev, E; Bergdahl, A; Zhao, XH; Sun, XY; Hedner, T; Edvinsson, L; Erlinge, D. (1999) Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure. Life Sci., 65 (11): 1195-206. [PMID:10503935]

12. Inscho, EW; Cook, AK; Imig, JD; Vial, C; Evans, RJ. (2003) Physiological role for P2X1 receptors in renal microvascular autoregulatory behavior. J. Clin. Invest., 112 (12): 1895-905. [PMID:14679185]

13. Jiang, L; Bardini, M; Keogh, A; dos Remedios, CG; Burnstock, G. (2005) P2X1 receptors are closely associated with connexin 43 in human ventricular myocardium. Int. J. Cardiol., 98 (2): 291-7. [PMID:15686781]

14. Kassack, MU; Braun, K; Ganso, M; Ullmann, H; Nickel, P; Böing, B; Müller, G; Lambrecht, G. (2004) Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist. Eur J Med Chem, 39 (4): 345-57. [PMID:15072843]

15. Khanam, T; Burnstock, G. (2007) Changes in expression of P2X1 receptors and connexin 43 in the rat myometrium during pregnancy. Fertil. Steril., 88 (4 Suppl): 1174-9. [PMID:17561003]

16. Lalo, U; Pankratov, Y; Wichert, SP; Rossner, MJ; North, RA; Kirchhoff, F; Verkhratsky, A. (2008) P2X1 and P2X5 subunits form the functional P2X receptor in mouse cortical astrocytes. J. Neurosci., 28 (21): 5473-80. [PMID:18495881]

17. Lamont, C; Vainorius, E; Wier, WG. (2003) Purinergic and adrenergic Ca2+ transients during neurogenic contractions of rat mesenteric small arteries. J. Physiol. (Lond.), 549 (Pt 3): 801-8. [PMID:12740429]

18. Lecut, C; Frederix, K; Johnson, DM; Deroanne, C; Thiry, M; Faccinetto, C; Marée, R; Evans, RJ; Volders, PG; Bours, V; et al.. (2009) P2X1 ion channels promote neutrophil chemotaxis through Rho kinase activation. J. Immunol., 183 (4): 2801-9. [PMID:19635923]

19. Lewis, CJ; Evans, RJ. (2001) P2X receptor immunoreactivity in different arteries from the femoral, pulmonary, cerebral, coronary and renal circulations. J. Vasc. Res., 38 (4): 332-40. [PMID:11455204]

20. Liang, SX; Jenkins, NA; Gilbert, DJ; Copeland, NG; Phillips, WD. (2001) Structure and chromosome location of the mouse P2X(1) purinoceptor gene (P2rx1). Cytogenet. Cell Genet., 92 (3-4): 333-6. [PMID:11435708]

21. Longhurst, PA; Schwegel, T; Folander, K; Swanson, R. (1996) The human P2x1 receptor: molecular cloning, tissue distribution, and localization to chromosome 17. Biochim. Biophys. Acta, 1308 (3): 185-8. [PMID:8809107]

22. Mironneau, J; Coussin, F; Morel, JL; Barbot, C; Jeyakumar, LH; Fleischer, S; Mironneau, C. (2001) Calcium signalling through nucleotide receptor P2X1 in rat portal vein myocytes. J. Physiol. (Lond.), 536 (Pt 2): 339-50. [PMID:11600670]

23. Mulryan, K; Gitterman, DP; Lewis, CJ; Vial, C; Leckie, BJ; Cobb, AL; Brown, JE; Conley, EC; Buell, G; Pritchard, CA; et al.. (2000) Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors. Nature, 403 (6765): 86-9. [PMID:10638758]

24. Nori, S; Fumagalli, L; Bo, X; Bogdanov, Y; Burnstock, G. (1998) Coexpression of mRNAs for P2X1, P2X2 and P2X4 receptors in rat vascular smooth muscle: an in situ hybridization and RT-PCR study. J. Vasc. Res., 35 (3): 179-85. [PMID:9647332]

25. O'Reilly, BA; Kosaka, AH; Chang, TK; Ford, AP; Popert, R; McMahon, SB. (2001) A quantitative analysis of purinoceptor expression in the bladders of patients with symptomatic outlet obstruction. BJU Int., 87 (7): 617-22. [PMID:11350400]

26. Ohkubo, T; Yamazaki, J; Nakashima, Y; Kitamura, K. (2000) Presence and possible role of the spliced isoform of the P2X1 receptor in rat vascular smooth muscle cells. Pflugers Arch., 441 (1): 57-64. [PMID:11205062]

27. Oury, C; Kuijpers, MJ; Toth-Zsamboki, E; Bonnefoy, A; Danloy, S; Vreys, I; Feijge, MA; De Vos, R; Vermylen, J; Heemskerk, JW; et al.. (2003) Overexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype. Blood, 101 (10): 3969-76. [PMID:12521992]

28. Oury, C; Toth-Zsamboki, E; Van Geet, C; Thys, C; Wei, L; Nilius, B; Vermylen, J; Hoylaerts, MF. (2000) A natural dominant negative P2X1 receptor due to deletion of a single amino acid residue. J. Biol. Chem., 275 (30): 22611-4. [PMID:10816552]

29. Rodrigues, R. J., Almeida, T., Richardson, P. J., Oliveira, C. R. and Cunha, R. A. (2005) Dual presynaptic control by ATP of glutamate release via facilitatory P2X1, P2X2/3, and P2X3 and inhibitory P2Y1, P2Y2, and/or P2Y4 receptors in the rat hippocampus. J Neurosci., 25: 6286-6295. [PMID:16000618]

30. Scase, TJ; Heath, MF; Allen, JM; Sage, SO; Evans, RJ. (1998) Identification of a P2X1 purinoceptor expressed on human platelets. Biochem. Biophys. Res. Commun., 242 (3): 525-8. [PMID:9464249]

31. Silva, AM; Rodrigues, RJ; Tomé, AR; Cunha, RA; Misler, S; Rosário, LM; Santos, RM. (2008) Electrophysiological and immunocytochemical evidence for P2X purinergic receptors in pancreatic beta cells. Pancreas, 36 (3): 279-83. [PMID:18362842]

32. Sim, JA; Park, CK; Oh, SB; Evans, RJ; North, RA. (2007) P2X1 and P2X4 receptor currents in mouse macrophages. Br. J. Pharmacol., 152 (8): 1283-90. [PMID:17934511]

33. Sluyter, R; Barden, JA; Wiley, JS. (2001) Detection of P2X purinergic receptors on human B lymphocytes. Cell Tissue Res., 304 (2): 231-6. [PMID:11396717]

34. Sánchez-Nogueiro, J; Marín-García, P; León, D; León-Otegui, M; Salas, E; Gómez-Villafuertes, R; Gualix, J; Miras-Portugal, MT. (2009) Axodendritic fibres of mouse cerebellar granule neurons exhibit a diversity of functional P2X receptors. Neurochem. Int., 55 (7): 671-82. [PMID:19560503]

35. Valera, S; Hussy, N; Evans, RJ; Adami, N; North, RA; Surprenant, A; Buell, G. (1994) A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP. Nature, 371 (6497): 516-9. [PMID:7523951]

36. Valera, S; Talabot, F; Evans, RJ; Gos, A; Antonarakis, SE; Morris, MA; Buell, GN. (1995) Characterization and chromosomal localization of a human P2X receptor from the urinary bladder. Recept. Channels, 3 (4): 283-9. [PMID:8834001]

37. Vial, C; Evans, RJ. (2000) P2X receptor expression in mouse urinary bladder and the requirement of P2X(1) receptors for functional P2X receptor responses in the mouse urinary bladder smooth muscle. Br. J. Pharmacol., 131 (7): 1489-95. [PMID:11090125]

38. Vial, C; Evans, RJ. (2001) Smooth muscle does not have a common P2x receptor phenotype: expression, ontogeny and function of P2x1 receptors in mouse ileum, bladder and reproductive systems. Auton Neurosci, 92 (1-2): 56-64. [PMID:11570704]

39. Vial, C; Evans, RJ. (2002) P2X(1) receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries. Mol. Pharmacol., 62 (6): 1438-45. [PMID:12435812]

40. Vial, C; Hechler, B; Léon, C; Cazenave, JP; Gachet, C. (1997) Presence of P2X1 purinoceptors in human platelets and megakaryoblastic cell lines. Thromb. Haemost., 78 (6): 1500-4. [PMID:9423802]

41. Vial, C; Rolf, MG; Mahaut-Smith, MP; Evans, RJ. (2002) A study of P2X1 receptor function in murine megakaryocytes and human platelets reveals synergy with P2Y receptors. Br. J. Pharmacol., 135 (2): 363-72. [PMID:11815371]

42. 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]

43. Vulchanova, L; Arvidsson, U; Riedl, M; Wang, J; Buell, G; Surprenant, A; North, RA; Elde, R. (1996) Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry. Proc. Natl. Acad. Sci. U.S.A., 93 (15): 8063-7. [PMID:8755603]

44. Wang, L; Andersson, M; Karlsson, L; Watson, MA; Cousens, DJ; Jern, S; Erlinge, D. (2003) Increased mitogenic and decreased contractile P2 receptors in smooth muscle cells by shear stress in human vessels with intact endothelium. Arterioscler. Thromb. Vasc. Biol., 23 (8): 1370-6. [PMID:12791671]

45. Wang, L; Karlsson, L; Moses, S; Hultgårdh-Nilsson, A; Andersson, M; Borna, C; Gudbjartsson, T; Jern, S; Erlinge, D. (2002) P2 receptor expression profiles in human vascular smooth muscle and endothelial cells. J. Cardiovasc. Pharmacol., 40 (6): 841-53. [PMID:12451317]

46. Wareham, K; Vial, C; Wykes, RC; Bradding, P; Seward, EP. (2009) Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells. Br. J. Pharmacol., 157 (7): 1215-24. [PMID:19552691]

To cite this database page, please use the following:

Richard J Evans.
P2X receptors: P2X1. Last modified on 01/04/2013. Accessed on 19/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=478.


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