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P2RX3  -  purinergic receptor P2X, ligand gated ion...

Homo sapiens

Synonyms: ATP receptor, P2X purinoceptor 3, P2X3, Purinergic receptor
 
 
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Disease relevance of P2RX3

 

High impact information on P2RX3

  • Some agonists (e.g., alphabeta-methylene ATP) and antagonists [e.g., 2',3'-O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3 subunits [6].
  • Moreover, ATP opens ligand-gated ion channels (P2X receptors) in sensory neurons and only sensory neurons express messenger RNA for the P2X3 receptor [7].
  • Nociceptors had currents that were similar to those of heterologously expressed channels containing P2X3 subunits, and had P2X3 immunoreactivity in their sensory endings and cell bodies [7].
  • Stretch receptors had currents that differed from those of P2X3 channels, and had no P2X3 immunoreactivity [7].
  • Here we report the cloning of a complementary DNA (P2X3) from rat dorsal root ganglia that had properties dissimilar to those of sensory neurons [8].
 

Chemical compound and disease context of P2RX3

 

Biological context of P2RX3

  • The full-length cDNA encodes a protein 397 amino acids long which shows a high amino-acid sequence identity with the rat P2X3 purinoceptor (93%) [11].
  • Tissue distribution analysis of human P2X3 receptor mRNA shows a restricted expression pattern, i.e. transcripts are limited to the spinal cord and heart [11].
  • By fluorescence in situ hybridization, the human P2X3 gene has been mapped to region q12 of chromosome 11 [11].
  • A-317491 potently blocked recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and was highly selective (IC50 >10 microM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes [12].
  • The efficiency of expression was improved by co-transfection with P2X2 and P2X3, when compared to transfection with the P2X3 subtype alone [13].
 

Anatomical context of P2RX3

  • Weaker P2X3-like immunoreactivity was also detected in fewer nerve fibers [14].
  • B lymphocytes are known to synthesise the P2X7 subtype of the P2X purinergic receptor family; however, the identification of the other six P2X subtypes on these cells has been limited by the absence of specific antibodies [15].
  • In RT-PCR, circular myocytes expressed mRNAs encoding P2X2, 3 and 4, while longitudinal myocytes expressed mRNAs for P2X3 and 5 [16].
  • However, immunohistochemistry demonstrated P2X1, but not P2X3, receptor immunoreactivity on the smooth muscle cells [17].
  • Heterologous expression of human P2X3 cRNA in Xenopus oocytes generates a fast desensitizing ATP-activated channel with pharmacological properties resembling the profile of the rat homologue receptor [11].
 

Associations of P2RX3 with chemical compounds

  • AIMS: To investigate the levels of the capsaicin or vanilloid receptor-1 (VR1) and the ATP-gated purinoceptor P2X3 in painful and nonpainful human tooth pulps [14].
  • Moreover, ATP-evoked currents on human P2X3 receptor are efficiently blocked in a reversible manner by the purinoceptor antagonists, suramin and PPADS [11].
  • Here, we show that intracellular Ca2+ mobilization via the purinergic receptor agonist ATP, the muscarinic receptor agonist carbachol or the Ca(2+)-ATPase inhibitor thapsigargin leads to formation of anandamide, and subsequent TRPV1-dependent Ca2+ influx in transfected cells and sensory neurons of rat dorsal root ganglia (DRG) [18].
  • To better characterize the release pathway(s) for IL-1beta and IL-18 we evaluated the role of lipopolysaccharide priming, of interleukin-1beta-converting enzyme (ICE) inhibition, of human purinergic receptor (P2X(7)) function, and of signaling pathways in human monocytes induced by ATP [19].
  • Following hints in the early literature about adenosine 5'-triphosphate (ATP) injections producing pain, an ion-channel nucleotide receptor was cloned in 1995, P2X3 subtype, which was shown to be localized predominantly on small nociceptive sensory nerves [20].
 

Other interactions of P2RX3

  • Each member of the family can form functional homomeric channels, but only P2X2 and P2X3 have been shown to combine to form a unique heteromeric channel [21].
  • Capsaicin receptor VR1 and ATP purinoceptor P2X3 in painful and nonpainful human tooth pulp [14].
  • In OSM-deficient mice, TRPV1/P2X3/OSMRbeta triple-positive neurons were significantly decreased [22].
  • RESULTS: The mRNA transcripts of most P2 receptors were detected in primary B cells; the expression of P2X3 and P2X7 receptors was the lowest of all the P2 receptors [23].
  • Absence of the responses of alphabeta-methylene ATP and 2-methylthio-ATP excluded functionally active P2X3, P2X4, and P2Y1 receptors as far as [Ca2+]i increase is concerned [24].
 

Analytical, diagnostic and therapeutic context of P2RX3

References

  1. Selective modulation of ligand-gated P2X purinoceptor channels by acute hypoxia is mediated by reactive oxygen species. Mason, H.S., Bourke, S., Kemp, P.J. Mol. Pharmacol. (2004) [Pubmed]
  2. Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Guo, A., Vulchanova, L., Wang, J., Li, X., Elde, R. Eur. J. Neurosci. (1999) [Pubmed]
  3. Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder. Yiangou, Y., Facer, P., Ford, A., Brady, C., Wiseman, O., Fowler, C.J., Anand, P. BJU international. (2001) [Pubmed]
  4. Baculovirus expression provides direct evidence for heteromeric assembly of P2X2 and P2X3 receptors. Radford, K.M., Virginio, C., Surprenant, A., North, R.A., Kawashima, E. J. Neurosci. (1997) [Pubmed]
  5. Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. Sun, Y., Chai, T.C. J. Urol. (2004) [Pubmed]
  6. Molecular physiology of P2X receptors. North, R.A. Physiol. Rev. (2002) [Pubmed]
  7. Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Cook, S.P., Vulchanova, L., Hargreaves, K.M., Elde, R., McCleskey, E.W. Nature (1997) [Pubmed]
  8. Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Lewis, C., Neidhart, S., Holy, C., North, R.A., Buell, G., Surprenant, A. Nature (1995) [Pubmed]
  9. The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. Amaya, F., Wang, H., Costigan, M., Allchorne, A.J., Hatcher, J.P., Egerton, J., Stean, T., Morisset, V., Grose, D., Gunthorpe, M.J., Chessell, I.P., Tate, S., Green, P.J., Woolf, C.J. J. Neurosci. (2006) [Pubmed]
  10. Monocyte-derived multinucleated giant cells and sarcoidosis. Okamoto, H., Mizuno, K., Horio, T. J. Dermatol. Sci. (2003) [Pubmed]
  11. Molecular characterization and pharmacological properties of the human P2X3 purinoceptor. Garcia-Guzman, M., Stühmer, W., Soto, F. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  12. 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. Jarvis, M.F., Burgard, E.C., McGaraughty, S., Honore, P., Lynch, K., Brennan, T.J., Subieta, A., Van Biesen, T., Cartmell, J., Bianchi, B., Niforatos, W., Kage, K., Yu, H., Mikusa, J., Wismer, C.T., Zhu, C.Z., Chu, K., Lee, C.H., Stewart, A.O., Polakowski, J., Cox, B.F., Kowaluk, E., Williams, M., Sullivan, J., Faltynek, C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  13. Characterization of Ca2+ influx through recombinant P2X receptor in C6BU-1 cells. Ueno, S., Koizumi, S., Inoue, K. Br. J. Pharmacol. (1998) [Pubmed]
  14. Capsaicin receptor VR1 and ATP purinoceptor P2X3 in painful and nonpainful human tooth pulp. Renton, T., Yiangou, Y., Baecker, P.A., Ford, A.P., Anand, P. Journal of orofacial pain. (2003) [Pubmed]
  15. Detection of P2X purinergic receptors on human B lymphocytes. Sluyter, R., Barden, J.A., Wiley, J.S. Cell Tissue Res. (2001) [Pubmed]
  16. Differential expression of P2X-purinoceptor subtypes in circular and longitudinal muscle of canine colon. Lee, H.K., Ro, S., Keef, K.D., Kathy, K.D., Kim, Y.H., Kim, H.W., Horowitz, B., Sanders, K.M. Neurogastroenterol. Motil. (2005) [Pubmed]
  17. The purinergic component of human vas deferens contraction. Banks, F.C., Knight, G.E., Calvert, R.C., Thompson, C.S., Morgan, R.J., Burnstock, G. Fertil. Steril. (2006) [Pubmed]
  18. Anandamide acts as an intracellular messenger amplifying Ca2+ influx via TRPV1 channels. van der Stelt, M., Trevisani, M., Vellani, V., De Petrocellis, L., Schiano Moriello, A., Campi, B., McNaughton, P., Geppetti, P., Di Marzo, V. EMBO J. (2005) [Pubmed]
  19. ATP-stimulated release of interleukin (IL)-1beta and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage. Mehta, V.B., Hart, J., Wewers, M.D. J. Biol. Chem. (2001) [Pubmed]
  20. Purinergic P2 receptors as targets for novel analgesics. Burnstock, G. Pharmacol. Ther. (2006) [Pubmed]
  21. Co-expression of P2X1 and P2X5 receptor subunits reveals a novel ATP-gated ion channel. Torres, G.E., Haines, W.R., Egan, T.M., Voigt, M.M. Mol. Pharmacol. (1998) [Pubmed]
  22. Oncostatin M in the development of the nervous system. Morikawa, Y. Anatomical science international / Japanese Association of Anatomists. (2005) [Pubmed]
  23. Expression of P2 receptors in human B cells and Epstein-Barr virus-transformed lymphoblastoid cell lines. Lee, D.H., Park, K.S., Kong, I.D., Kim, J.W., Han, B.G. BMC Immunol. (2006) [Pubmed]
  24. Membrane-specific expression of functional purinergic receptors in normal human nasal epithelial cells. Kim, C.H., Kim, S.S., Choi, J.Y., Shin, J.H., Kim, J.Y., Namkung, W., Lee, J.G., Lee, M.G., Yoon, J.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  25. TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics. Honore, P., Mikusa, J., Bianchi, B., McDonald, H., Cartmell, J., Faltynek, C., Jarvis, M.F. Pain (2002) [Pubmed]
 
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