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P2rx3  -  purinergic receptor P2X, ligand-gated ion...

Rattus norvegicus

Synonyms: ATP receptor, P2X purinoceptor 3, P2X3, Purinergic receptor
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Disease relevance of P2rx3

  • We found that endogenously active CaMKII up-regulates basal P2X3 receptor activity in dorsal root ganglion neurons [1].
  • Furthermore, P2X3 localizes in raft-containing fractions in transiently transfected SH-SY5Y neuroblastoma cells [2].
  • Its efficacy demonstrates the importance of peripheral P2X3/P2X(2/3) receptors in mediating ATP-associated mechanical hyperalgesia following inflammation, confirming previous suggestions of a significant role for P2X(2/3) [3].
  • Hence, alpha,beta-meATP-sensitive P2X3 and/or P2X2/3 receptors of L6/S1 dorsal root ganglion neurons were functionally downregulated during subacute pain caused by experimental cystitis [4].
  • Thus, it is suggested that the activation of the P2X3 receptor is involved in the phosphorylation of ERK in DRG neurons and the mechanical hypersensitivity of the inflamed knee joint [5].

Psychiatry related information on P2rx3

  • P2X3 receptor blockade raised the pressure and volume thresholds for the reflex, whereas P2X1 receptor blockade diminished motor activity associated with voiding [6].

High impact information on P2rx3


Chemical compound and disease context of P2rx3


Biological context of P2rx3

  • IP5I blocked alphabeta-methylene ATP (alphabeta-meATP)-evoked P2X3 responses in a concentration-dependent manner (IC50 = 0.6 +/- 0.1 microM) [12].
  • These results suggest that TNP-ATP acts as a competitive antagonist and competes with alphabeta-meATP at the P2X3 agonist binding site [12].
  • Developmental downregulation of P2X3 receptors in motoneurons of the compact formation of the nucleus ambiguus [13].
  • Heterogeneity in ATP current kinetics occurs even though immunocytochemical staining reveals a relatively homogeneous and widespread expression of the P2X2 and P2X3 subunits [14].
  • Using inactivation protocols, we demonstrate the presence of homomeric P2X3-like receptors and non-inactivating P2X receptors, which indicates that individual subsets of adult dorsal root ganglion neurons have distinct P2X receptor phenotypes, and that individual DRG neurons may express multiple P2X receptor subtypes [15].

Anatomical context of P2rx3

  • We provide direct biochemical evidence that P2X3 receptor localizes into lipid rafts, in primary cultures of cerebellar granule neurons as well as in brain and dorsal root ganglia extracts [2].
  • Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochlea [16].
  • Taken together, these results indicate that noradrenergic terminals of the rat hippocampus are equipped with presynaptic facilitatory P2X receptors, displaying a pharmacological profile similar to homomeric P2X1 and P2X3 receptors [17].
  • These studies demonstrate plastic expression of P2X2 and P2X3 receptors in bladder and spinal cord during early postnatal development at times coincident with appearance of mature voiding patterns [18].
  • Development of nerves expressing P2X3 receptors in the myenteric plexus of rat stomach [19].

Associations of P2rx3 with chemical compounds

  • The former effect was mimicked by a P2X3 agonist, alpha,beta-methylene ATP, at 10(-5) M, while the latter was mimicked by 2-methylthio ADP (a P2Y1 agonist) or UTP (a P2Y2 agonist) at 10(-3) M, suggesting that the former is mediated by P2X receptors and the latter by P2Y receptors [20].
  • Superfusion of the selective P2X1, P2X3 and P2X(2/3) receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (6-638 microM) partially blocked the Vc central sensitization [21].
  • 5. These results suggest that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X2 and P2X3 [22].
  • 3 Phenol red (a P2X1/P2X3 antagonist; 0.1 and 1 micromol kg(-1)) caused a significant increase in the pressure and volume thresholds required to initiate a reflex and, at the higher dose, also caused a reduction in postinfusion isovolumetric contractions [6].
  • 5 It is concluded that P2X1 and P2X3 receptors play a fundamental role in the micturition reflex in urethane-anesthetized female rats [6].

Co-localisations of P2rx3


Regulatory relationships of P2rx3


Other interactions of P2rx3


Analytical, diagnostic and therapeutic context of P2rx3

  • Here we report the molecular cloning and characterization of a new member of the P2X receptor family, P2X3, expressed by these cells [7].
  • Western analyses indicate that electrical stimulation enhances the expression of P2X3 receptors in the membrane and that the enhancement is blocked by the inhibitor [1].
  • We studied the activity of the noncompetitive antagonist P1, P5-di[inosine-5'] pentaphosphate (IP5I) at the P2X3 receptor, compared with the well studied competitive antagonist TNP-ATP, using a whole-cell voltage-clamp technique in dissociated rat DRG neurons [12].
  • Western blot of whole bladders for P2X2 and P2X3 expression was performed [18].
  • 5. Using confocal immunofluorescence, co-localization of P2X2 and P2X3 protein was demonstrated in many petrosal somas and CB afferent terminals in situ [30].


  1. Ca2+/calmodulin-dependent protein kinase II potentiates ATP responses by promoting trafficking of P2X receptors. Xu, G.Y., Huang, L.Y. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. P2X3 receptor localizes into lipid rafts in neuronal cells. Vacca, F., Amadio, S., Sancesario, G., Bernardi, G., Volonté, C. J. Neurosci. Res. (2004) [Pubmed]
  3. A-317491, a selective P2X3/P2X2/3 receptor antagonist, reverses inflammatory mechanical hyperalgesia through action at peripheral receptors in rats. Wu, G., Whiteside, G.T., Lee, G., Nolan, S., Niosi, M., Pearson, M.S., Ilyin, V.I. Eur. J. Pharmacol. (2004) [Pubmed]
  4. Subsensitivity of P2X but not vanilloid 1 receptors in dorsal root ganglia of rats caused by cyclophosphamide cystitis. Borvendeg, S.J., Al-Khrasani, M., Rubini, P., Fischer, W., Allgaier, C., Wirkner, K., Himmel, H.M., Gillen, C., Illes, P. Eur. J. Pharmacol. (2003) [Pubmed]
  5. The role of ERK signaling and the P2X receptor on mechanical pain evoked by movement of inflamed knee joint. Seino, D., Tokunaga, A., Tachibana, T., Yoshiya, S., Dai, Y., Obata, K., Yamanaka, H., Kobayashi, K., Noguchi, K. Pain (2006) [Pubmed]
  6. Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetized rats. King, B.F., Knowles, I.D., Burnstock, G., Ramage, A.G. Br. J. Pharmacol. (2004) [Pubmed]
  7. A P2X purinoceptor expressed by a subset of sensory neurons. Chen, C.C., Akopian, A.N., Sivilotti, L., Colquhoun, D., Burnstock, G., Wood, J.N. Nature (1995) [Pubmed]
  8. P2Y1 purinergic receptors in sensory neurons: contribution to touch-induced impulse generation. Nakamura, F., Strittmatter, S.M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. Collo, G., North, R.A., Kawashima, E., Merlo-Pich, E., Neidhart, S., Surprenant, A., Buell, G. J. Neurosci. (1996) [Pubmed]
  10. The suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benzenesulfonic acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic acid groups. Hausmann, R., Rettinger, J., Gerevich, Z., Meis, S., Kassack, M.U., Illes, P., Lambrecht, G., Schmalzing, G. Mol. Pharmacol. (2006) [Pubmed]
  11. Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons. Gerevich, Z., Müller, C., Illes, P. Eur. J. Pharmacol. (2005) [Pubmed]
  12. The P2X3 antagonist P1, P5-di[inosine-5'] pentaphosphate binds to the desensitized state of the receptor in rat dorsal root ganglion neurons. Ford, K.K., Matchett, M., Krause, J.E., Yu, W. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  13. Developmental downregulation of P2X3 receptors in motoneurons of the compact formation of the nucleus ambiguus. Brosenitsch, T.A., Adachi, T., Lipski, J., Housley, G.D., Funk, G.D. Eur. J. Neurosci. (2005) [Pubmed]
  14. Adenosine triphosphate-evoked currents in cultured dorsal root ganglion neurons obtained from rat embryos: desensitization kinetics and modulation of glutamate release. Labrakakis, C., Gerstner, E., MacDermott, A.B. Neuroscience (2000) [Pubmed]
  15. Characterization of cultured dorsal root ganglion neuron P2X receptors. Grubb, B.D., Evans, R.J. Eur. J. Neurosci. (1999) [Pubmed]
  16. Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochlea. Huang, L.C., Greenwood, D., Thorne, P.R., Housley, G.D. J. Comp. Neurol. (2005) [Pubmed]
  17. P2X receptor activation elicits transporter-mediated noradrenaline release from rat hippocampal slices. Papp, L., Balázsa, T., Köfalvi, A., Erdélyi, F., Szabó, G., Vizi, E.S., Sperlágh, B. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  18. P2X2 and P2X3 receptor expression in postnatal and adult rat urinary bladder and lumbosacral spinal cord. Studeny, S., Torabi, A., Vizzard, M.A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  19. Development of nerves expressing P2X3 receptors in the myenteric plexus of rat stomach. Xiang, Z., Burnstock, G. Histochem. Cell Biol. (2004) [Pubmed]
  20. Inhibitory, facilitatory, and excitatory effects of ATP and purinergic receptor agonists on the activity of rat cutaneous nociceptors in vitro. Yajima, H., Sato, J., Giron, R., Nakamura, R., Mizumura, K. Neurosci. Res. (2005) [Pubmed]
  21. Endogenous ATP involvement in mustard-oil-induced central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn). Chiang, C.Y., Zhang, S., Xie, Y.F., Hu, J.W., Dostrovsky, J.O., Salter, M.W., Sessle, B.J. J. Neurophysiol. (2005) [Pubmed]
  22. Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons. Ueno, S., Tsuda, M., Iwanaga, T., Inoue, K. Br. J. Pharmacol. (1999) [Pubmed]
  23. Intraganglionic laminar endings in the rat esophagus contain purinergic P2X2 and P2X3 receptor immunoreactivity. Wang, Z.J., Neuhuber, W.L. Anat. Embryol. (2003) [Pubmed]
  24. P2X2 and P2X3 purinoceptors in the rat enteric nervous system. Xiang, Z., Burnstock, G. Histochem. Cell Biol. (2004) [Pubmed]
  25. P2X receptors in sensory neurones. Burnstock, G. British journal of anaesthesia. (2000) [Pubmed]
  26. Functional ATP receptors in rat anterior pituitary cells. Villalobos, C., Alonso-Torre, S.R., Núñez, L., García-Sancho, J. Am. J. Physiol. (1997) [Pubmed]
  27. P2 receptors in the thymus: expression of P2X and P2Y receptors in adult rats, an immunohistochemical and in situ hybridisation study. Glass, R., Townsend-Nicholson, A., Burnstock, G. Cell Tissue Res. (2000) [Pubmed]
  28. Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones. Shibuya, I., Tanaka, K., Hattori, Y., Uezono, Y., Harayama, N., Noguchi, J., Ueta, Y., Izumi, F., Yamashita, H. J. Physiol. (Lond.) (1999) [Pubmed]
  29. Presence of diverse functional P2X receptors in rat cerebellar synaptic terminals. Hervás, C., Pérez-Sen, R., Miras-Portugal, M.T. Biochem. Pharmacol. (2005) [Pubmed]
  30. Expression of P2X2 and P2X3 receptor subunits in rat carotid body afferent neurones: role in chemosensory signalling. Prasad, M., Fearon, I.M., Zhang, M., Laing, M., Vollmer, C., Nurse, C.A. J. Physiol. (Lond.) (2001) [Pubmed]
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