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Gene Review

P2rx1  -  purinergic receptor P2X, ligand-gated ion...

Mus musculus

Synonyms: AI323649, ATP receptor, BB122383, P2X purinoceptor 1, P2X1, ...
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Disease relevance of P2rx1

  • A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo [1].
  • The mortality of P2X1-/- mice in a model of systemic thromboembolism was reduced and the size of mural thrombi formed after a laser-induced vessel wall injury was decreased as compared with normal mice, whereas the time for complete thrombus removal was shortened [1].
  • We have cloned mouse candidate cell death genes RP-2 and nedd2 and used Northern blot analysis to study their expression in a growth-factor-dependent cell line (FDC-P1) that can be induced to undergo apoptosis by growth factor withdrawal and in a thymoma line (ST4) that undergoes apoptosis when irradiated [2].

High impact information on P2rx1

  • In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists are abolished [3].
  • The P2X1 receptor is a fast ATP-gated cation channel expressed in blood platelets, where its role has been difficult to assess due to its rapid desensitization and the lack of pharmacological tools [1].
  • Given that two of the tumor clones, A149 and A166, are remarkably similar in amino acid and DNA sequence to H-2Lq and H-2Dq, respectively, we also examined the 1591 RP2 and GUS loci for evidence of polymorphism [4].
  • Deletion analysis and heterologous promoter assay disclosed that the proximal promoter region from -75 to +16 was able to activate chloramphenicol acetyltransferase expression by cAMP, and indicated that the proximal promoter element from -75 to -47 (RP-2 element) overlapping the TATA-like region was able to confer cAMP responsiveness [5].
  • In inbred mice (Mus domesticus), the concentrations of mRNAs encoded by RP2 undergo a 10- to 12-fold induction in response to testosterone; in other Mus species (e.g., Mus hortulanus and Mus caroli), induction ranges from none to about two- to fourfold [6].

Biological context of P2rx1


Anatomical context of P2rx1

  • ATP activates P2x-contracting and P2y-relaxing purinoceptors in the smooth muscle of mouse vas deferens [11].
  • A study of P2X1 receptor function in murine megakaryocytes and human platelets reveals synergy with P2Y receptors [12].
  • With conditions below thresholds for classical electroporation and apoptosis, nsPEF induced calcium release from intracellular stores and subsequent calcium influx through store-operated channels in the plasma membrane that mimicked purinergic receptor-mediated calcium mobilization [13].
  • Contractile responses were reduced by > 80% in the ileum from P2x1 receptor-deficient mice. alpha,beta-meATP-evoked contractions were reduced by approximately 35% by TTX (1 microM) and were unaffected by atropine (10 microM) [14].
  • Gel shift assay identified RU-1 element-binding factors in both 293 and HeLa cells, whereas 293 cell-dominant factors were shown to bind only to RP-2 element [15].

Associations of P2rx1 with chemical compounds

  • A subpopulation of neurons (10-15%) were alpha,beta-methylene ATP (alpha,beta-meATP) sensitive, and in neurons from P2X1 receptor-deficient mice the alpha,beta-meATP response was reduced to 2% of all neurons, demonstrating a direct role for P2X1 subunits [16].
  • Control alpha,beta-meATP responses were eliminated by high extracellular Ca(2+) and pH, indicating the presence of heteromeric channels incorporating the properties of P2X1 and P2X2 receptors [16].
  • Other nucleotides tested, including beta, gamma-methylene-ATP and 2-methylthio-ATP, which are considered prototypic agonists for P2x and P2y receptors, respectively, were ineffective; in general, modifications in the ribose-triphosphate chain and substitution on the 2-position of the purines reduced the efficacy of nucleotides [17].
  • Topical application of suramin (nonspecific ATP receptor antagonist), pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (P2X receptor antagonist), and 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) (P2X1, P2X3, P2X2/3 antagonist) after barrier disruption accelerated the barrier repair [18].
  • In platelets, the classical P2T receptor has now been resolved into three P2 receptor subtypes: the P2Y1, P2X1 and P2TAC receptors (the last of these, which is coupled to the inhibition of adenylate cyclase, is yet to be cloned) [19].

Other interactions of P2rx1


Analytical, diagnostic and therapeutic context of P2rx1

  • Immunofluorescence staining of the vas deferens with antibodies against P2X1 receptor showed a diffuse, grainy distribution over the entire membrane of each smooth muscle cell [23].
  • Electrophoretic mobility shift assay and DNase I footprinting analysis demonstrated that novel nuclear factors in 293 cells interacted with the RP-2 element, and that cAMP increased the binding activity of these nuclear factors to the RP-2 element [5].
  • With rat LH-RP-2 (rLH) used as the standard diluted in assay buffer, the LH ELISA had a sensitivity of 102 pg/ml and a 50% displacement point of 531 pg/ml [24].
  • Modification of the mouse interstitial cell testosterone assay by the addition of 1.5 microM forskolin to the incubation medium has improved the sensitivity of this luteinizing hormone bioassay from approximately 100 to 3 pg/tube of NIH rLH RP-2 [25].


  1. A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo. Hechler, B., Lenain, N., Marchese, P., Vial, C., Heim, V., Freund, M., Cazenave, J.P., Cattaneo, M., Ruggeri, Z.M., Evans, R., Gachet, C. J. Exp. Med. (2003) [Pubmed]
  2. Expression of candidate cell death genes in cell lines during apoptosis. Häcker, G., Vaux, D.L. Biochem. Cell Biol. (1994) [Pubmed]
  3. Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors. Mulryan, K., Gitterman, D.P., Lewis, C.J., Vial, C., Leckie, B.J., Cobb, A.L., Brown, J.E., Conley, E.C., Buell, G., Pritchard, C.A., Evans, R.J. Nature (2000) [Pubmed]
  4. The tumor-rejection antigens of the 1591 ultraviolet fibrosarcoma. Potential origin and evolutionary implications. Linsk, R., Watts, S., Fischer, A., Goodenow, R.S. J. Exp. Med. (1989) [Pubmed]
  5. Mechanism of cAMP regulation of renin gene transcription by proximal promoter. Tamura, K., Umemura, S., Yamaguchi, S., Iwamoto, T., Kobayashi, S., Fukamizu, A., Murakami, K., Ishii, M. J. Clin. Invest. (1994) [Pubmed]
  6. Molecular genetics of androgen-inducible RP2 gene transcription in the mouse kidney. Rheaume, C., Barbour, K.W., Tseng-Crank, J., Berger, F.G. Mol. Cell. Biol. (1989) [Pubmed]
  7. Structure and chromosome location of the mouse P2X(1) purinoceptor gene (P2rx1). Liang, S.X., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Phillips, W.D. Cytogenet. Cell Genet. (2001) [Pubmed]
  8. Inhibition of platelet functions and thrombosis through selective or nonselective inhibition of the platelet P2 receptors with increasing doses of NF449 [4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis-(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid octasodium salt]. Hechler, B., Magnenat, S., Zighetti, M.L., Kassack, M.U., Ullmann, H., Cazenave, J.P., Evans, R., Cattaneo, M., Gachet, C. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  9. Cloning, tissue distribution and functional characterization of the chicken P2X1 receptor. Soto, F., Krause, U., Borchardt, K., Ruppelt, A. FEBS Lett. (2003) [Pubmed]
  10. ADP receptors--targets for developing antithrombotic agents. Kunapuli, S.P., Ding, Z., Dorsam, R.T., Kim, S., Murugappan, S., Quinton, T.M. Curr. Pharm. Des. (2003) [Pubmed]
  11. ATP activates P2x-contracting and P2y-relaxing purinoceptors in the smooth muscle of mouse vas deferens. Boland, B., Himpens, B., Vincent, M.F., Gillis, J.M., Casteels, R. Br. J. Pharmacol. (1992) [Pubmed]
  12. A study of P2X1 receptor function in murine megakaryocytes and human platelets reveals synergy with P2Y receptors. Vial, C., Rolf, M.G., Mahaut-Smith, M.P., Evans, R.J. Br. J. Pharmacol. (2002) [Pubmed]
  13. Diverse effects of nanosecond pulsed electric fields on cells and tissues. Beebe, S.J., White, J., Blackmore, P.F., Deng, Y., Somers, K., Schoenbach, K.H. DNA Cell Biol. (2003) [Pubmed]
  14. Smooth muscles does not have a common P2x receptor phenotype: expression, ontogeny and function of P2x1 receptors in mouse ileum, bladder and reproductive systems. Vial, C., Evans, R.J. Autonomic neuroscience : basic & clinical. (2001) [Pubmed]
  15. A combination of upstream and proximal elements is required for efficient expression of the mouse renin promoter in cultured cells. Tamura, K., Tanimoto, K., Murakami, K., Fukamizu, A. Nucleic Acids Res. (1992) [Pubmed]
  16. Heterogeneity of P2X receptors in sympathetic neurons: contribution of neuronal P2X1 receptors revealed using knockout mice. Calvert, J.A., Evans, R.J. Mol. Pharmacol. (2004) [Pubmed]
  17. Purinergic receptor regulation of signal transduction in NCB-20 cells. Garritsen, A., Zhang, Y., Cooper, D.M. Mol. Pharmacol. (1992) [Pubmed]
  18. P2X purinergic receptor antagonist accelerates skin barrier repair and prevents epidermal hyperplasia induced by skin barrier disruption. Denda, M., Inoue, K., Fuziwara, S., Denda, S. J. Invest. Dermatol. (2002) [Pubmed]
  19. P2 receptor subtypes in the cardiovascular system. Kunapuli, S.P., Daniel, J.L. Biochem. J. (1998) [Pubmed]
  20. Purinergic receptor ligands stimulate pro-opiomelanocortin gene expression in AtT-20 pituitary corticotroph cells. Zhao, L.F., Iwasaki, Y., Oki, Y., Tsugita, M., Taguchi, T., Nishiyama, M., Takao, T., Kambayashi, M., Hashimoto, K. J. Neuroendocrinol. (2006) [Pubmed]
  21. P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Coutinho-Silva, R., Persechini, P.M., Bisaggio, R.D., Perfettini, J.L., Neto, A.C., Kanellopoulos, J.M., Motta-Ly, I., Dautry-Varsat, A., Ojcius, D.M. Am. J. Physiol. (1999) [Pubmed]
  22. A differential role of the platelet ADP receptors P2Y1 and P2Y12 in Rac activation. Soulet, C., Hechler, B., Gratacap, M.P., Plantavid, M., Offermanns, S., Gachet, C., Payrastre, B. J. Thromb. Haemost. (2005) [Pubmed]
  23. Spatial distribution and developmental appearance of postjunctional P2X1 receptors on smooth muscle cells of the mouse vas deferens. Liang, S.X., Motin, L., Moussa, C.E., Lavidis, N.A., Phillips, W.D. Synapse (2001) [Pubmed]
  24. Development of a sensitive enzyme-linked immunosorbent assay for cattle, sheep, rat, and mouse luteinizing hormone. Spearow, J.L., Trost, B.A. Biol. Reprod. (1987) [Pubmed]
  25. Improved sensitivity of the mouse interstitial cell testosterone assay with the addition of forskolin. Debertin, W.J., Pomerantz, D.K. Can. J. Physiol. Pharmacol. (1992) [Pubmed]
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