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Gene Review

P2ry2  -  purinergic receptor P2Y, G-protein coupled 2

Mus musculus

Synonyms: ATP receptor, P2U purinoceptor 1, P2U1, P2Y purinoceptor 2, P2Y2, ...
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Disease relevance of P2ry2


High impact information on P2ry2

  • Pressure-induced increases in membrane capacitance (a measure of apical plasma membrane surface area where 1 microF approximately equals 1 cm2) were inhibited by the serosal, but not mucosal, addition of apyrase or the purinergic receptor antagonist PPADS [5].
  • This purinergic receptor has been described chiefly in cells of hemopoietic origin such as T cells, thymocytes, monocytes, macrophages, and phagocytic cells of thymic reticulum [6].
  • These results suggest that during inflammatory conditions, IL-1beta reveals a functional P2Y2 signaling pathway in astrocytes that results in a dramatic increase in the levels of free AA [7].
  • ATP receptor mediated Ca2+ signaling was recorded from Bergmann glial cells in cerebellar slices obtained from mice of different ages (postnatal days 6 to 45) [8].
  • 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 [9].

Biological context of P2ry2


Anatomical context of P2ry2

  • In summary, these results indicate that both the P2Y2 and P2Y4 receptors are present in the luminal membrane of mouse distal colonic mucosa, and stimulation of these receptors leads to K+ secretion [10].
  • Taken together, these results point to the presence of functional P2Y1 (ADP), P2Y2 (ATP, UTP) and P2Y6 (UDP) receptors on murine aorta endothelial cells [15].
  • Thoracic aorta segments (width 2 mm) of P2Y2-deficient and wild-type (WT) mice were mounted in organ baths to measure isometric force development and intracellular calcium signalling.Relaxations evoked by ADP, UDP and acetylcholine were identical in knockout and WT mice, indicating that the receptors for these agonists function normally [16].
  • We have used two-electrode voltage-clamp analysis and ion substitution to further characterize these P2z purinergic receptor-induced currents as expressed in mRNA-injected oocytes [17].
  • 6 These results indicate the presence of several P2Y receptors coupled to an increase in intracellular calcium in the SCG: ADP-sensitive P2Y1 receptors and UDP-sensitive P2Y6 receptors in SCG neurons and glial cells, a novel UTP-sensitive P2Y receptor in SCG neurons and UTP- and ATP-sensitive P2Y2 receptors in SCG glia [18].

Associations of P2ry2 with chemical compounds

  • The luminal UTP-stimulated K+ secretion was still present in P2Y2 receptor knock-out mice, but significantly reduced (DeltaV(te): 0.83 +/- 0.26 mV) compared to wild-type littermates (DeltaV(te): 2.08 +/- 0.52 mV, n = 9) [10].
  • Furthermore, in vitro and in vivo administration of purinergic receptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) blocked the expression of HSP25 immunoreactivity in sustentacular cells [19].
  • P2Y2-deficient mice showed impaired ATP- and adenosine 5'[gamma-thio] triphosphate (ATPgammaS)-evoked relaxation, suggesting that in WT mice, ATP and ATPgammaS activate predominantly the P2Y2 subtype [16].
  • The P2U purinoceptor-selective agonist UTP and the P2Y purinoceptor-selective agonist ADP beta S induce inositol 1,4,5-trisphosphate generation in a concentration-dependent manner with maximal effective concentrations of approximately 100 microM [20].
  • The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion [21].

Other interactions of P2ry2

  • Luminal UTP-stimulated K+ secretion was completely absent in P2Y2/P2Y4 double receptor KO mice [10].
  • Pharmacological screening with purinergic ligands indicated the presence of P2Y1 and P2Y2/4 receptors linked to the activation of a K+ current and P2X receptors, including P2X7, linked to the activation of a nonselective cationic current [22].
  • For UTP, it was unclear whether P2Y2, P2Y6 or yet another subtype was involved [16].
  • The former, but not the latter, was inhibited by U-73122, indicating that the former was via the P2Y2 receptor and the latter via the P2X7 receptor [23].
  • Use of the polymerase chain reaction coupled with reverse transcription showed that mouse clonal early proximal tubule (S1) cell line (NF-5) and outer medullary collecting tubule (OMCT) cells expressed mRNA for P2X4, P2Y1 and P2Y2 purinoceptors [24].

Analytical, diagnostic and therapeutic context of P2ry2

  • Coexpression of TRPV1 mRNA with P2Y2 mRNA, but not P2Y1 mRNA, was determined in the rat lumbar DRG using in situ hybridization histochemistry [1].
  • Transcripts of the purinergic receptor P2Y2 subtype were amplified by polymerase chain reaction from the cDNA of granulosa cells or cumulus cells [25].
  • Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y1/P2Y2-/- mice relative to wild-type mice [2].
  • 4. ATP and UTP applied to either the apical or the basolateral bath equi-potently stimulated ISC while 'purified' ADP and UDP had no effect consistent with P2Y2 purinoceptors, the expression of which was confirmed using RT-PCR [26].
  • In a co-culture of NHEKs and DRG neurons, mechanical-stimulation-evoked Ca2+ waves in NHEKs caused an increase in [Ca2+]i in the adjacent DRG neurons, which was also dependent on extracellular ATP and the activation of P2Y2 receptors [27].


  1. Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity. Moriyama, T., Iida, T., Kobayashi, K., Higashi, T., Fukuoka, T., Tsumura, H., Leon, C., Suzuki, N., Inoue, K., Gachet, C., Noguchi, K., Tominaga, M. J. Neurosci. (2003) [Pubmed]
  2. Increased susceptibility of purinergic receptor-deficient mice to lung infection with Pseudomonas aeruginosa. Geary, C., Akinbi, H., Korfhagen, T., Fabre, J.E., Boucher, R., Rice, W. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  3. P2Y2 nucleotide receptor up-regulation in submandibular gland cells from the NOD.B10 mouse model of Sjögren's syndrome. Schrader, A.M., Camden, J.M., Weisman, G.A. Arch. Oral Biol. (2005) [Pubmed]
  4. Cystic fibrosis transmembrane regulator-independent release of ATP. Its implications for the regulation of P2Y2 receptors in airway epithelia. Watt, W.C., Lazarowski, E.R., Boucher, R.C. J. Biol. Chem. (1998) [Pubmed]
  5. ATP and purinergic receptor-dependent membrane traffic in bladder umbrella cells. Wang, E.C., Lee, J.M., Ruiz, W.G., Balestreire, E.M., von Bodungen, M., Barrick, S., Cockayne, D.A., Birder, L.A., Apodaca, G. J. Clin. Invest. (2005) [Pubmed]
  6. Pharmacologic properties of P(2Z)/P2X(7 )receptor characterized in murine dendritic cells: role on the induction of apoptosis. Nihei, O.K., de Carvalho, A.C., Savino, W., Alves, L.A. Blood (2000) [Pubmed]
  7. Interleukin-1 enhances the ATP-evoked release of arachidonic acid from mouse astrocytes. Stella, N., Estellés, A., Siciliano, J., Tencé, M., Desagher, S., Piomelli, D., Glowinski, J., Prémont, J. J. Neurosci. (1997) [Pubmed]
  8. ATP-induced cytoplasmic calcium mobilization in Bergmann glial cells. Kirischuk, S., Möller, T., Voitenko, N., Kettenmann, H., Verkhratsky, A. J. Neurosci. (1995) [Pubmed]
  9. 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]
  10. K+ secretion activated by luminal P2Y2 and P2Y4 receptors in mouse colon. Matos, J.E., Robaye, B., Boeynaems, J.M., Beauwens, R., Leipziger, J. J. Physiol. (Lond.) (2005) [Pubmed]
  11. 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]
  12. Nucleotide-regulated calcium signaling in lung fibroblasts and epithelial cells from normal and P2Y(2) receptor (-/-) mice. Homolya, L., Watt, W.C., Lazarowski, E.R., Koller, B.H., Boucher, R.C. J. Biol. Chem. (1999) [Pubmed]
  13. Purinergic receptor regulation of signal transduction in NCB-20 cells. Garritsen, A., Zhang, Y., Cooper, D.M. Mol. Pharmacol. (1992) [Pubmed]
  14. The P2Y agonist UTP activates cutaneous afferent fibers. Stucky, C.L., Medler, K.A., Molliver, D.C. Pain (2004) [Pubmed]
  15. Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta. Guns, P.J., Korda, A., Crauwels, H.M., Van Assche, T., Robaye, B., Boeynaems, J.M., Bult, H. Br. J. Pharmacol. (2005) [Pubmed]
  16. Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2-deficient mice. Guns, P.J., Van Assche, T., Fransen, P., Robaye, B., Boeynaems, J.M., Bult, H. Br. J. Pharmacol. (2006) [Pubmed]
  17. Differential activation of cation channels and non-selective pores by macrophage P2z purinergic receptors expressed in Xenopus oocytes. Nuttle, L.C., Dubyak, G.R. J. Biol. Chem. (1994) [Pubmed]
  18. Evidence for P2Y1, P2Y2, P2Y6 and atypical UTP-sensitive receptors coupled to rises in intracellular calcium in mouse cultured superior cervical ganglion neurons and glia. Calvert, J.A., Atterbury-Thomas, A.E., Leon, C., Forsythe, I.D., Gachet, C., Evans, R.J. Br. J. Pharmacol. (2004) [Pubmed]
  19. Purinergic receptor antagonists inhibit odorant-induced heat shock protein 25 induction in mouse olfactory epithelium. Hegg, C.C., Lucero, M.T. Glia (2006) [Pubmed]
  20. Two distinct P2 purinergic receptors, P2Y and P2U, are coupled to phospholipase C in mouse pineal gland tumor cells. Suh, B.C., Son, J.H., Joh, T.H., Kim, K.T. J. Neurochem. (1997) [Pubmed]
  21. The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion. Ghanem, E., Robaye, B., Leal, T., Leipziger, J., Van Driessche, W., Beauwens, R., Boeynaems, J.M. Br. J. Pharmacol. (2005) [Pubmed]
  22. Purinergic receptors on microglial cells: functional expression in acute brain slices and modulation of microglial activation in vitro. Boucsein, C., Zacharias, R., Färber, K., Pavlovic, S., Hanisch, U.K., Kettenmann, H. Eur. J. Neurosci. (2003) [Pubmed]
  23. Effects of anions on ATP-induced [Ca2+], increase in NG108-15 cells. Watano, T., Matsuoka, I., Ogawa, K., Kimura, J. Jpn. J. Pharmacol. (2002) [Pubmed]
  24. Establishment of a mouse clonal early proximal tubule cell line and outer medullary collecting duct cells expressing P2 purinoceptors. Takeda, M., Kobayashi, M., Endou, H. Biochem. Mol. Biol. Int. (1998) [Pubmed]
  25. Ionic currents activated via purinergic receptors in the cumulus cell-enclosed mouse oocyte. Arellano, R.O., Martínez-Torres, A., Garay, E. Biol. Reprod. (2002) [Pubmed]
  26. ATP stimulates Cl- secretion and reduces amiloride-sensitive Na+ absorption in M-1 mouse cortical collecting duct cells. Cuffe, J.E., Bielfeld-Ackermann, A., Thomas, J., Leipziger, J., Korbmacher, C. J. Physiol. (Lond.) (2000) [Pubmed]
  27. Ca2+ waves in keratinocytes are transmitted to sensory neurons: the involvement of extracellular ATP and P2Y2 receptor activation. Koizumi, S., Fujishita, K., Inoue, K., Shigemoto-Mogami, Y., Tsuda, M., Inoue, K. Biochem. J. (2004) [Pubmed]
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