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Gene Review

P2ry12  -  purinergic receptor P2Y, G-protein coupled...

Rattus norvegicus

Synonyms: P2Y purinoceptor 12, P2Y12, P2Y12 platelet ADP receptor, P2y12
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Disease relevance of P2ry12

  • Our data suggest that secretion of endogenous ADP and subsequent P2Y12-mediated signaling are critical for platelet aggregation, platelet spreading, and as a consequence, for stabilization of thrombus [1].
  • Previously it was shown that stimulation of the P2Y12 receptor activates PKB signalling in C6 glioma cells [K. Van Kolen and H. Slegers, J. Neurochem. 89, 442.]. In the present study, the mechanisms involved in this response were further elucidated [2].

High impact information on P2ry12

  • The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts [3].
  • In addition, we showed the predominant association of P2Y12 oligomers to cell membrane lipid rafts and the partitioning of P2Y12 out of rafts in response to clopidogrel and Act-Met [3].
  • Finally, using a series of receptors individually mutated at each cysteine residue and a chimeric P2Y12/P2Y13 receptor, we pointed out the involvement of cysteine 97 within the first extracellular loop of P2Y12 in the mechanism of action of Act-Met [3].
  • P2Y12, a G protein-coupled receptor that plays a central role in platelet activation has been recently identified as the receptor targeted by the antithrombotic drug, clopidogrel [3].
  • The raft-associated P2Y12 oligomers represented the functional form of the receptor, as demonstrated by binding and signal transduction studies [3].

Biological context of P2ry12


Anatomical context of P2ry12


Associations of P2ry12 with chemical compounds

  • P2Y12 receptor stimulation inhibits beta-adrenergic receptor-induced differentiation by reversing the cyclic AMP-dependent inhibition of protein kinase B [8].
  • To investigate how P2Y receptors are activated in a neuronal environment, we used PC12 cells in which nucleotides were found to elicit increases in inositol phosphates via P2Y2 and decreases in cAMP via P2Y12 receptors [9].
  • These results indicate that nucleoside diphosphate-sensitive (P2Y12 and P2Y1) receptors are activated by spontaneous nucleotide release, whereas triphosphate-sensitive (P2Y2) receptors require an excess of depolarization-evoked release to become activated [9].

Other interactions of P2ry12

  • 5. In conclusion, the data suggest that P2Y (P2Y1 or P2Y12) receptor subtypes are involved in the generation of astrogliosis in the NAc of rats, with a possible minor contribution of P2X receptor subtypes [10].

Analytical, diagnostic and therapeutic context of P2ry12


  1. Impaired platelet function in a patient with P2Y12 deficiency caused by a mutation in the translation initiation codon. Shiraga, M., Miyata, S., Kato, H., Kashiwagi, H., Honda, S., Kurata, Y., Tomiyama, Y., Kanakura, Y. J. Thromb. Haemost. (2005) [Pubmed]
  2. P2Y12 receptor signalling towards PKB proceeds through IGF-I receptor cross-talk and requires activation of Src, Pyk2 and Rap1. Van Kolen, K., Gilany, K., Moens, L., Esmans, E.L., Slegers, H. Cell. Signal. (2006) [Pubmed]
  3. The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts. Savi, P., Zachayus, J.L., Delesque-Touchard, N., Labouret, C., Hervé, C., Uzabiaga, M.F., Pereillo, J.M., Culouscou, J.M., Bono, F., Ferrara, P., Herbert, J.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Involvement of beta1 integrin in microglial chemotaxis and proliferation on fibronectin: different regulations by ADP through PKA. Nasu-Tada, K., Koizumi, S., Inoue, K. Glia (2005) [Pubmed]
  5. Differential effects of P2Y1 and P2Y12 nucleotide receptors on ERK1/ERK2 and phosphatidylinositol 3-kinase signalling and cell proliferation in serum-deprived and nonstarved glioma C6 cells. Czajkowski, R., Banachewicz, W., Ilnytska, O., Drobot, L.B., Baranska, J. Br. J. Pharmacol. (2004) [Pubmed]
  6. Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Sasaki, Y., Hoshi, M., Akazawa, C., Nakamura, Y., Tsuzuki, H., Inoue, K., Kohsaka, S. Glia (2003) [Pubmed]
  7. Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y receptor-mediated inhibition of voltage-gated Ca2+ channels. Lechner, S.G., Dorostkar, M.M., Mayer, M., Edelbauer, H., Pankevych, H., Boehm, S. Eur. J. Neurosci. (2004) [Pubmed]
  8. P2Y12 receptor stimulation inhibits beta-adrenergic receptor-induced differentiation by reversing the cyclic AMP-dependent inhibition of protein kinase B. Van Kolen, K., Slegers, H. J. Neurochem. (2004) [Pubmed]
  9. Activity-dependent autocrine-paracrine activation of neuronal P2Y receptors. Moskvina, E., Unterberger, U., Boehm, S. J. Neurosci. (2003) [Pubmed]
  10. P2 receptor-types involved in astrogliosis in vivo. Franke, H., Krügel, U., Schmidt, R., Grosche, J., Reichenbach, A., Illes, P. Br. J. Pharmacol. (2001) [Pubmed]
  11. 2-Alkylthio-substituted platelet P2Y12 receptor antagonists reveal pharmacological identity between the rat brain Gi-linked ADP receptors and P2Y12. Vasiljev, K.S., Uri, A., Laitinen, J.T. Neuropharmacology (2003) [Pubmed]
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