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Gene Review

P2rx6  -  purinergic receptor P2X, ligand-gated ion...

Rattus norvegicus

Synonyms: ATP receptor, P2X purinoceptor 6, P2X6, P2XM, P2rxl1, ...
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Disease relevance of P2rxl1

  • Short-term hyperthyroidism modulates the fat-cell adenylate cyclase system at the receptor level (beta-receptor number increased, R-site purinergic-receptor number decreased) and the catalytic subunit of adenylate cyclase [1].
  • Its effect on phospholipase C seems to be mediated by a purinergic receptor coupled to the intracellular effector via a pertussis toxin-sensitive G protein [2].

High impact information on P2rxl1

  • When intracellular Ca2+ levels are increased or decreased in C cells, by the calcium ionophore A23187, by physiologic concentrations of the P2 purinergic receptor ligand ATP, or by changes in extracellular Ca2+ levels, the promoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or increased [3].
  • These characteristics are consistent with a heterogeneous population of P2X receptors, the composition of which includes P2X2, P2X4, and P2X6 receptor subtypes [4].
  • Two new P2X receptor cDNAs (P2X5 and P2X6) were isolated and expressed [5].
  • P2X2, P2X4, and P2X6, are the most abundant in the dorsal horn [5].
  • Since ADP, AMP, and adenosine (in descending order) were less potent or ineffective in inducing the cation conductance, the involvement of a P2 purinergic receptor is proposed [6].

Biological context of P2rxl1

  • The rat P2X6 nucleotide sequence encodes a 379 amino acid protein that conserves all the structural features of previously cloned P2X receptors, including the two putative transmembrane domains predicted by hydrophobicity plots [7].
  • It is speculated that P2X7 receptors may be involved in programmed cell death during embryogenesis and that P2X4, P2X(5) and P2X6 receptors might be involved in postnatal neurogenesis [8].
  • To examine whether leptin synthesis and lipolysis are influenced by P2 purinergic receptor activation, the effects of ATP and other nucleotides on leptin secretion and glycerol release have been investigated in differentiated rat white adipocytes [9].
  • Functional regulation of P2X6 receptors by N-linked glycosylation: identification of a novel alpha beta-methylene ATP-sensitive phenotype [10].
  • Purinergic receptor expression in the regeneration epidermis in a rat model of normal and delayed wound healing [11].

Anatomical context of P2rxl1

  • Injection of P2X6 cRNA in Xenopus oocytes did not give rise to ATP-activated channels [7].
  • P2X5 receptors were seen in the differentiating cell layers of the stratified squamous vaginal epithelium and also in the very early stages of ovarian follicular development; P2X6 receptors were present in secondary follicles [12].
  • P2X2 and 3 receptors were abundant on medullary epithelial cells, whilst P2X6 receptors were prominent in Hassall's corpuscles [13].
  • Molecular-biological methods were used to demonstrate the expression of six P2X receptor subunits (P2X1-P2X6) in retina and choroid [14].
  • Antibodies to P2X3 reacted with nerve fibres in the adventitia of vas deferens, and the P2X6 receptor was localised in the basal lamina of the epithelium [15].

Associations of P2rxl1 with chemical compounds

  • P2X6 receptors, like P2X4, receptors, are not blocked by the antagonists suramin and pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid [5].
  • The order of their potencies was ATP >> 2-MeSATP > or = ADP > adenosine > AMP, corresponding to a P2 purinergic receptor [16].
  • Purinergic receptor agonists such as ADP, AMP adenosine, and 2-methylthio ATP (2-MeSATP) also evoked similar outward currents [16].
  • ATP-gated currents were also markedly potentiated by toluene in cells transfected with both P2X4 and P2X6 subunits [17].
  • Moreover, the observation that fluoride mimicked the inhibitory action of ATP suggests the activation of G proteins during purinergic receptor stimulation [18].

Other interactions of P2rxl1

  • Immunoreactivity for P2X1 and P2X6 was mainly confined to somatic areas of S100beta-positive cells, whereas the subunit P2X3 was primarily localized along astroglial processes [19].
  • We further examined the coexpression of all pairs of P2X2-P2X6 mRNAs in DRG neurons and found that: 1) P2X4 was always present in combination with the other subunits [20].

Analytical, diagnostic and therapeutic context of P2rxl1

  • 7. In situ hybridization revealed that the P2X receptor transcripts levels in rat MPG neurons are P2X2>P2X4>P2X1, P2X3, P2X5 and P2X6 [21].
  • Analysis of hippocampal protein expression by two-dimensional electrophoresis (2DE) revealed increased expression of the P2X6 purinergic receptor in the zinc-restricted rats, as determined by MALDI mass spectrometry (MS) and database analysis [22].
  • Microinjections of alpha, beta-methylene ATP (alpha,beta-MeATP), a selective P2x purinergic receptor agonist, or 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), a selective A2a adenosine (P1) receptor agonist, were made into the subpostremal region of the NTS via multibarrel glass micropipettes [23].
  • P2X1-P2X6 purinoceptors were detected by immunohistochemistry [24].


  1. Short-term hyperthyroidism modulates adenosine receptors and catalytic activity of adenylate cyclase in adipocytes. Rapiejko, P.J., Malbon, C.C. Biochem. J. (1987) [Pubmed]
  2. Direct effect of adenosine on prolactin secretion at the level of the single rat lactotroph: involvement of pertussis toxin-sensitive and -insensitive transducing mechanisms. Scorziello, A., Landolfi, E., Grimaldi, M., Meucci, O., Ventra, C., Avallone, A., Postiglione, A., Schettini, G. J. Mol. Endocrinol. (1993) [Pubmed]
  3. Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells. Suzuki, K., Lavaroni, S., Mori, A., Okajima, F., Kimura, S., Katoh, R., Kawaoi, A., Kohn, L.D. Mol. Cell. Biol. (1998) [Pubmed]
  4. ATP P2X receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord. Bardoni, R., Goldstein, P.A., Lee, C.J., Gu, J.G., MacDermott, A.B. J. Neurosci. (1997) [Pubmed]
  5. 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]
  6. Extracellular ATP activates a cation conductance and a K+ conductance in cultured microglial cells from mouse brain. Walz, W., Ilschner, S., Ohlemeyer, C., Banati, R., Kettenmann, H. J. Neurosci. (1993) [Pubmed]
  7. Cloning and tissue distribution of a novel P2X receptor from rat brain. Soto, F., Garcia-Guzman, M., Karschin, C., Stühmer, W. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  8. Expression of P2X purinoceptors during rat brain development and their inhibitory role on motor axon outgrowth in neural tube explant cultures. Cheung, K.K., Chan, W.Y., Burnstock, G. Neuroscience (2005) [Pubmed]
  9. Dual roles of P2 purinergic receptors in insulin-stimulated leptin production and lipolysis in differentiated rat white adipocytes. Lee, H., Jun, D.J., Suh, B.C., Choi, B.H., Lee, J.H., Do, M.S., Suh, B.S., Ha, H., Kim, K.T. J. Biol. Chem. (2005) [Pubmed]
  10. Functional regulation of P2X6 receptors by N-linked glycosylation: identification of a novel alpha beta-methylene ATP-sensitive phenotype. Jones, C.A., Vial, C., Sellers, L.A., Humphrey, P.P., Evans, R.J., Chessell, I.P. Mol. Pharmacol. (2004) [Pubmed]
  11. Purinergic receptor expression in the regeneration epidermis in a rat model of normal and delayed wound healing. Greig, A.V., James, S.E., McGrouther, D.A., Terenghi, G., Burnstock, G. Exp. Dermatol. (2003) [Pubmed]
  12. Distribution of P2X receptor subtypes in the rat female reproductive tract at late pro-oestrus/early oestrus. Bardini, M., Lee, H.Y., Burnstock, G. Cell Tissue Res. (2000) [Pubmed]
  13. 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]
  14. Gene expression of the P2X receptors in the rat retina. Brändle, U., Guenther, E., Irrle, C., Wheeler-Schilling, T.H. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  15. P2X receptor immunoreactivity in the male genital organs of the rat. Lee, H.Y., Bardini, M., Burnstock, G. Cell Tissue Res. (2000) [Pubmed]
  16. ATP-evoked potassium currents in rat striatal neurons are mediated by a P2 purinergic receptor. Ikeuchi, Y., Nishizaki, T. Neurosci. Lett. (1995) [Pubmed]
  17. Effects of the abused solvent toluene on recombinant P2X receptors expressed in HEK293 cells. Woodward, J.J., Nowak, M., Davies, D.L. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  18. Extracellular ATP inhibits the small-conductance K channel on the apical membrane of the cortical collecting duct from mouse kidney. Lu, M., MacGregor, G.G., Wang, W., Giebisch, G. J. Gen. Physiol. (2000) [Pubmed]
  19. Distribution of P2X receptors on astrocytes in juvenile rat hippocampus. Kukley, M., Barden, J.A., Steinhäuser, C., Jabs, R. Glia (2001) [Pubmed]
  20. Differential expression patterns of mRNAs for P2X receptor subunits in neurochemically characterized dorsal root ganglion neurons in the rat. Kobayashi, K., Fukuoka, T., Yamanaka, H., Dai, Y., Obata, K., Tokunaga, A., Noguchi, K. J. Comp. Neurol. (2005) [Pubmed]
  21. Pharmacological and molecular characterization of P2X receptors in rat pelvic ganglion neurons. Zhong, Y., Dunn, P.M., Xiang, Z., Bo, X., Burnstock, G. Br. J. Pharmacol. (1998) [Pubmed]
  22. Expression of P2X6, a purinergic receptor subunit, is affected by dietary zinc deficiency in rat hippocampus. Chu, Y., Mouat, M.F., Coffield, J.A., Orlando, R., Grider, A. Biological trace element research. (2003) [Pubmed]
  23. Activation of purinergic receptor subtypes in the nucleus tractus solitarius elicits specific regional vascular response patterns. Barraco, R.A., O'Leary, D.S., Ergene, E., Scislo, T.J. J. Auton. Nerv. Syst. (1996) [Pubmed]
  24. P2X purinoceptor subtypes on paraventricular nucleus neurones projecting to the rostral ventrolateral medulla in the rat. Cham, J.L., Owens, N.C., Barden, J.A., Lawrence, A.J., Badoer, E. Exp. Physiol. (2006) [Pubmed]
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