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Gene Review

P2RY6  -  pyrimidinergic receptor P2Y, G-protein...

Homo sapiens

Synonyms: P2Y purinoceptor 6, P2Y6, PP2891
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Disease relevance of P2RY6


High impact information on P2RY6

  • Transfection of lung epithelial cells with antisense oligonucleotides targeting specific purinergic P2Y receptors revealed that the P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating HNP-induced IL-8 production [6].
  • These events were mediated primarily by P2Y receptors, specifically the P2Y2 and/or P2Y6 subclass of receptors [7].
  • Agonist-promoted regulation of the uridine nucleotide-activated human P2Y4 receptor (P2Y4-R) and P2Y6 receptor (P2Y6-R) was studied [8].
  • This receptor, designated P2Y7, has 352 amino acids and shares 23-30% amino acid identity with the P2Y1-P2Y6 purinoceptors [9].
  • The P2Y6-receptor has a widespread distribution including heart, blood vessels, and brain [10].

Chemical compound and disease context of P2RY6


Biological context of P2RY6


Anatomical context of P2RY6


Associations of P2RY6 with chemical compounds

  • Neuronal differentiation of the cells by treatment with retinoic acid for 7 days did not change the expression level of P2Y6 receptors [1].
  • The nucleotide efficacy profile [ATP = ADP > UDP >or= UTP > adenosine >or= 2-methylthioadenosine-5'-diphosphate, with alpha,beta-methylene adenosine 5'-triphosphate, 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, AMP, UMP, and ATPalphaS inactive] and PCR analysis indicate involvement of P2Y2 and P2Y6 receptors [19].
  • 3. Inositol trisphosphates assays have identified a response typical of the P2Y2 receptor in the 1HAEo- and the 16HBE14o- airway epithelial cell lines which co-express P2Y2 and P2Y6 mRNA [20].
  • These results define the uridine nucleotide selectivity of three phospholipase C-linked receptors: a receptor that is selectively activated by UDP (P2Y6 receptor), selectively activated by UTP (P2Y4 receptor), and activated by UTP and ATP but not by diphosphate nucleotides (P2Y2 receptor) [21].
  • Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors [22].

Other interactions of P2RY6

  • Expressions of P2Y2 and P2Y6 receptors in NHNE cells were further verified by immunoblotting using specific antibodies [16].
  • With the recent discovery of several new members from a variety of species, the P2Y purinoceptor family now encompasses types P2Y1 to P2Y6 [12].
  • The human P2Y6 receptor (hP2Y6) is a member of the G protein-coupled pyrimidinergic P2 receptor family that responds specifically to the extracellular nucleotide uridine diphosphate (UDP) [2].
  • UDP activation of P2Y6 provoked: (a) an increase in free cytosolic calcium; (b) the activation of protein kinase C-alpha, -beta, -delta, -epsilon, and -zeta but not of PKC-iota and -eta; (c) the phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2); (d) the expression of c-Fos protein [23].
  • In smooth muscle cells (SMCs), high shear stress decreased P2X1 receptors, whereas P2Y2 and P2Y6 receptors were upregulated [24].

Analytical, diagnostic and therapeutic context of P2RY6


  1. Attenuation of signal flow from P2Y6 receptor by protein kinase C-alpha in SK-N-BE(2)C human neuroblastoma cells. Lee, H., Choi, B.H., Suh, B.C., Lee, S.K., Kim, K.T. J. Neurochem. (2003) [Pubmed]
  2. The pyrimidinergic P2Y6 receptor mediates a novel release of proinflammatory cytokines and chemokines in monocytic cells stimulated with UDP. Cox, M.A., Gomes, B., Palmer, K., Du, K., Wiekowski, M., Wilburn, B., Petro, M., Chou, C.C., Desquitado, C., Schwarz, M., Lunn, C., Lundell, D., Narula, S.K., Zavodny, P.J., Jenh, C.H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  3. Expression of the P2Y6 purinergic receptor in human T cells infiltrating inflammatory bowel disease. Somers, G.R., Hammet, F.M., Trute, L., Southey, M.C., Venter, D.J. Lab. Invest. (1998) [Pubmed]
  4. Potent P2Y6 receptor mediated contractions in human cerebral arteries. Malmsjö, M., Hou, M., Pendergast, W., Erlinge, D., Edvinsson, L. BMC Pharmacol. (2003) [Pubmed]
  5. Pharmacological and second messenger signalling selectivities of cloned P2Y receptors. Nicholas, R.A., Lazarowski, E.R., Watt, W.C., Li, Q., Boyer, J., Harden, T.K. Journal of autonomic pharmacology. (1996) [Pubmed]
  6. Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway. Khine, A.A., Del Sorbo, L., Vaschetto, R., Voglis, S., Tullis, E., Slutsky, A.S., Downey, G.P., Zhang, H. Blood (2006) [Pubmed]
  7. Extracellular ATP-mediated signaling for survival in hyperoxia-induced oxidative stress. Ahmad, S., Ahmad, A., Ghosh, M., Leslie, C.C., White, C.W. J. Biol. Chem. (2004) [Pubmed]
  8. Differential regulation of the uridine nucleotide-activated P2Y4 and P2Y6 receptors. SER-333 and SER-334 in the carboxyl terminus are involved in agonist-dependent phosphorylation desensitization and internalization of the P2Y4 receptor. Brinson, A.E., Harden, T.K. J. Biol. Chem. (2001) [Pubmed]
  9. Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells. Akbar, G.K., Dasari, V.R., Webb, T.E., Ayyanathan, K., Pillarisetti, K., Sandhu, A.K., Athwal, R.S., Daniel, J.L., Ashby, B., Barnard, E.A., Kunapuli, S.P. J. Biol. Chem. (1996) [Pubmed]
  10. Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. von Kügelgen, I. Pharmacol. Ther. (2006) [Pubmed]
  11. P2Y6 nucleotide receptor activates PKC to protect 1321N1 astrocytoma cells against tumor necrosis factor-induced apoptosis. Kim, S.G., Gao, Z.G., Soltysiak, K.A., Chang, T.S., Brodie, C., Jacobson, K.A. Cell. Mol. Neurobiol. (2003) [Pubmed]
  12. Chromosomal localization of the human P2y6 purinoceptor gene and phylogenetic analysis of the P2y purinoceptor family. Somers, G.R., Hammet, F., Woollatt, E., Richards, R.I., Southey, M.C., Venter, D.J. Genomics (1997) [Pubmed]
  13. Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues. Maier, R., Glatz, A., Mosbacher, J., Bilbe, G. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  14. Colocalization of P2Y2 and P2Y6 receptor genes at human chromosome 11q13.3-14.1. Pidlaoan, L.V., Jin, J., Sandhu, A.K., Athwal, R.S., Kunapuli, S.P. Somat. Cell Mol. Genet. (1997) [Pubmed]
  15. CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors. Mamedova, L., Capra, V., Accomazzo, M.R., Gao, Z.G., Ferrario, S., Fumagalli, M., Abbracchio, M.P., Rovati, G.E., Jacobson, K.A. Biochem. Pharmacol. (2005) [Pubmed]
  16. 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]
  17. Molecular pharmacology of P2Y-receptors. von Kügelgen, I., Wetter, A. Naunyn Schmiedebergs Arch. Pharmacol. (2000) [Pubmed]
  18. Characterization of the biological activities of uridine diphosphate in human dendritic cells: Influence on chemotaxis and CXCL8 release. Idzko, M., Panther, E., Sorichter, S., Herouy, Y., Berod, L., Geissler, M., Mockenhaupt, M., Elsner, P., Girolomoni, G., Norgauer, J. J. Cell. Physiol. (2004) [Pubmed]
  19. ATP- and UTP-activated P2Y receptors differently regulate proliferation of human lung epithelial tumor cells. Schafer, R., Sedehizade, F., Welte, T., Reiser, G. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  20. Expression of P2Y receptors in cell lines derived from the human lung. Communi, D., Paindavoine, P., Place, G.A., Parmentier, M., Boeynaems, J.M. Br. J. Pharmacol. (1999) [Pubmed]
  21. Uridine nucleotide selectivity of three phospholipase C-activating P2 receptors: identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor. Nicholas, R.A., Watt, W.C., Lazarowski, E.R., Li, Q., Harden, K. Mol. Pharmacol. (1996) [Pubmed]
  22. Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors. Kim, S.G., Soltysiak, K.A., Gao, Z.G., Chang, T.S., Chung, E., Jacobson, K.A. Biochem. Pharmacol. (2003) [Pubmed]
  23. Differential signalling of purinoceptors in HeLa cells through the extracellular signal-regulated kinase and protein kinase C pathways. Muscella, A., Greco, S., Elia, M.G., Storelli, C., Marsigliante, S. J. Cell. Physiol. (2004) [Pubmed]
  24. Increased mitogenic and decreased contractile P2 receptors in smooth muscle cells by shear stress in human vessels with intact endothelium. Wang, L., Andersson, M., Karlsson, L., Watson, M.A., Cousens, D.J., Jern, S., Erlinge, D. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  25. Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues. Maier, R., Glatz, A., Mosbacher, J., Bilbe, G. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  26. Activation of P2Y2 purinoceptor inhibits the activity of the Na+/K+-ATPase in HeLa cells. Muscella, A., Elia, M.G., Greco, S., Storelli, C., Marsigliante, S. Cell. Signal. (2003) [Pubmed]
  27. Positive inotropic effects by uridine triphosphate (UTP) and uridine diphosphate (UDP) via P2Y2 and P2Y6 receptors on cardiomyocytes and release of UTP in man during myocardial infarction. Wihlborg, A.K., Balogh, J., Wang, L., Borna, C., Dou, Y., Joshi, B.V., Lazarowski, E., Jacobson, K.A., Arner, A., Erlinge, D. Circ. Res. (2006) [Pubmed]
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