P2X1

Target id: 478

Nomenclature: P2X1

Family: P2X receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     P2X1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 399 17p13.3 P2RX1 purinergic receptor P2X 1 42
Mouse 2 399 11 B4 P2rx1 purinergic receptor P2X, ligand-gated ion channel, 1 24
Rat 2 399 10q24 P2rx1 purinergic receptor P2X 1 41
Previous and Unofficial Names
P2XR1 | P2X purinoceptor 1 | P2X1 receptor | Pdcd3 | purinergic receptor P2X, ligand gated ion channel, 1
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
ATP

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

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
ATP Hs Agonist 7.3 pEC50 15
pEC50 7.3 (EC50 5.6x10-8 M) [15]
BzATP Hs Full agonist - -
αβ-meATP Hs Full agonist - -
L-βγ-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 48
pIC50 ~8.9 (IC50 ~1.3x10-9 M) [48]
Ip5I Hs Antagonist ~8.5 pIC50
pIC50 ~8.5 (IC50 ~3.2x10-9 M)
NF023 Hs Antagonist ~6.7 pIC50
pIC50 ~6.7 (IC50 ~2x10-7 M)
NF449 Hs Antagonist ~6.3 pIC50 18
pIC50 ~6.3 (IC50 ~5x10-7 M) [18]
suramin Rn Antagonist 6.0 pIC50 15
pIC50 6.0 (IC50 1x10-6 M) [15]
View species-specific antagonist tables
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
MRS 2219 Hs Positive - - - no 16
[16]
Not voltage dependent
Immunopharmacology Comments
Functional P2X1 receptors are expressed by healthy human eosinophils [53]. In these cells P2X1 receptor activation is involved in αMβ2 integrin-dependent adhesion. Responses of eosinophils from asthmatic patients are reduced, potentially by increased extracellular nucleotide concentration as detected in bronchoalveolar lavage fluids from patients with airway inflammations [8,13,25,34].
Immuno Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
Comment: 
References:  53
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  serotonin secretion by platelet (GO:0002554) IEA
neutrophil degranulation (GO:0043312) TAS
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  neutrophil degranulation (GO:0043312) TAS
References: 
Tissue Distribution
Blood cells; platelets, mast cells, lymphocytes
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, Western blot
References:  36,39,46,52
Smooth muscle; bladder, vas deferens, arteries
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, Northern blot, RT-PCR, Western Blot
References:  2,4,26,42,51
Heart tissue.
Expression level:  Medium
Species:  Human
Technique:  Immunohistochemistry, Western blotting, RT-PCR
References:  3,12,17
Macrophages, neutrophils, megakaryocytes/platelts, pancreatic beta cells
Expression level:  Medium
Species:  Mouse
Technique:  Immunohistochemistry, Knockouts
References:  22,37-38,47
Astrocytes, cerebellar granule neurons
Expression level:  Medium
Species:  Mouse
Technique:  RT-PCR
References:  20,40
Smooth muscle; vas deferens, bladder, arteries
Expression level:  High
Species:  Mouse
Technique:  Immunohistochemistry
References:  28,43-45
Smooth muscle; vas deferens, bladder, arteries, portal vein, myometrium
Expression level:  High
Species:  Rat
Technique:  Immunohistochemistry and in situ hybridisation.
References:  5-6,19,23,27,29,41,49
Spinal cord, superior cervical ganalion, sensory ganglia, hippocampal neurons
Expression level:  Medium
Species:  Rat
Technique:  in situ hybridisation, RT-PCR
References:  5-6,19,23,27,29,35
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
Male infertility
Species:  Mouse
Tissue:  Vas deferens
Technique:  Knock out
References:  28
Reduced nerve evoked bladder contraction
Species:  Mouse
Tissue:  Urinary (bladder)
Technique:  Knock out
References:  43
Reduced nerve evoked artery contraction
Species:  Mouse
Tissue:  Mesenteric artery
Technique:  knock out
References:  21,45
Reduced kidney autoregulation of blood flow
Species:  Mouse
Tissue:  Kidney arterioles
Technique:  knock out
References:  14
Decreased mortality in thromboembolism models
Species:  Mouse
Tissue:  Platelets
Technique:  Knock out
References:  7,11
Increased mortality in thromboembolism models
Species:  Mouse
Tissue:  Platelets
Technique:  megakaryocyte specific over-expression
References:  32
Reduced ATP evoked P2X receptor currents in macrophages
Species:  Mouse
Tissue:  Macrophages
Technique:  Knock out
References:  38
Physiological Consequences of Altering Gene Expression Comments
P2X1 receptor knockout mice also reveal a role for the receptors in neutrophil chemotaxis [22]
Gene Expression and Pathophysiology
Upregulation
Tissue or cell type:  Heart
Pathophysiology:  Congestive heart failure
Species:  Human
Technique:  RT-PCR
References:  12
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:  50
Upregulation
Tissue or cell type:  Urinary-bladder
Pathophysiology:  Outlet obstruction
Species:  Human
Technique:  RT-PCR
References:  30
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  P2X1del (deletion:176-192)
References:  9
Type:  Splice variant
Species:  Human
Description:  P2X1del (deletion:346-379)
References:  10
Type:  Splice variant
Species:  Human
Description:  P2X1delL (deletion:353)
References:  33
Type:  Splice variant
Species:  Rat
Description:  P2X1a receptor isoform (deletion:175-201)
Amino acids:  372
Nucleotide accession: 
Protein accession: 
References:  31
General Comments
An alternatively spliced variant of the rat P2X1 subunit, provisionally termed p2X1a which lacks function as a homomer has been described [31]. An inactive, naturally occurring human mutant dominant negative P2X receptor has also been reported [33].

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. Electrophoresis20 (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. Esther Jr CR, Alexis NE, Clas ML, Lazarowski ER, Donaldson SH, Ribeiro CM, Moore CG, Davis SD, Boucher RC. (2008) Extracellular purines are biomarkers of neutrophilic airway inflammation. Eur. Respir. J.31 (5): 949-56. [PMID:18256064]

9. 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. Blood98 (1): 100-7. [PMID:11418468]

10. 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]

11. 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]

12. 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]

13. Idzko M, Hammad H, van Nimwegen M, Kool M, Willart MA, Muskens F, Hoogsteden HC, Luttmann W, Ferrari D, Di Virgilio F et al.. (2007) Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat. Med.13 (8): 913-9. [PMID:17632526]

14. 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]

15. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J. Med. Chem.45 (19): 4057-93. [PMID:12213051]

16. Jacobson KA, Kim YC, Wildman SS, Mohanram A, Harden TK, Boyer JL, King BF, Burnstock G. (1998) A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate and antagonize activation of P2X1 receptors. J. Med. Chem.41 (13): 2201-6. [PMID:9632352]

17. 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]

18. 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 Chem39 (4): 345-57. [PMID:15072843]

19. 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]

20. 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]

21. 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]

22. 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]

23. 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]

24. 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]

25. Lommatzsch M, Cicko S, Müller T, Lucattelli M, Bratke K, Stoll P, Grimm M, Dürk T, Zissel G, Ferrari D et al.. (2010) Extracellular adenosine triphosphate and chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.181 (9): 928-34. [PMID:20093639]

26. Longhurst PA, Schwegel T, Folander K, Swanson R. (1996) The human P2x1 receptor: molecular cloning, tissue distribution, and localization to chromosome 17. Biochim. Biophys. Acta1308 (3): 185-8. [PMID:8809107]

27. 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]

28. 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. Nature403 (6765): 86-9. [PMID:10638758]

29. 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]

30. 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]

31. 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]

32. 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. Blood101 (10): 3969-76. [PMID:12521992]

33. 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]

34. Riteau N, Gasse P, Fauconnier L, Gombault A, Couegnat M, Fick L, Kanellopoulos J, Quesniaux VF, Marchand-Adam S, Crestani B et al.. (2010) Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am. J. Respir. Crit. Care Med.182 (6): 774-83. [PMID:20522787]

35. Rodrigues RJ, Almeida T, Richardson PJ, Oliveira CR, Cunha RA. (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]

36. 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]

37. 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. Pancreas36 (3): 279-83. [PMID:18362842]

38. 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]

39. 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]

40. 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]

41. 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. Nature371 (6497): 516-9. [PMID:7523951]

42. 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. Channels3 (4): 283-9. [PMID:8834001]

43. 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]

44. 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 Neurosci92 (1-2): 56-64. [PMID:11570704]

45. 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]

46. 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]

47. 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]

48. 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]

49. 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]

50. 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]

51. 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]

52. 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]

53. Wright A, Mahaut-Smith M, Symon F, Sylvius N, Ran S, Bafadhel M, Muessel M, Bradding P, Wardlaw A, Vial C. (2016) Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients. J. Immunol.196 (12): 4877-84. [PMID:27183585]

Contributors

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How to cite this page

Richard J Evans.
P2X receptors: P2X1. Last modified on 07/02/2017. Accessed on 23/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=478.