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Gene Review

P2RY1  -  purinergic receptor P2Y, G-protein coupled, 1

Homo sapiens

Synonyms: ATP receptor, P2Y purinoceptor 1, P2Y1, Purinergic receptor
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Disease relevance of P2RY1

  • A3P5PS, A3P5P, and adenosine-2',5'-diphosphate also were competitive antagonists in studies with the cloned human P2Y1 receptor stably expressed in 1321N1 human astrocytoma cells [1].
  • The action of extracellular nucleotides on P2Y receptors was shown to mediate the growth of melanomas and the P2Y1 receptor is a putative target for melanoma therapy [2].
  • Pharmacotherapy of the ion transport defect in cystic fibrosis: role of purinergic receptor agonists and other potential therapeutics [3].
  • We conclude that LPA at concentrations approaching those found in vivo can induce platelet shape change, aggregation, and platelet-monocyte aggregate formation in whole blood and suggest that antagonists of platelet P2Y1 and P2Y12 receptors might be useful preventing LPA-elicited thrombus formation in patients with cardiovascular diseases [4].
  • Consistent with the expression of G protein-coupled P2Y receptors in skeletal tissue, the human osteosarcoma cell line SaOS-2 and primary osteoblasts express P2Y1 and P2Y2 receptors, respectively [5].

Psychiatry related information on P2RY1


High impact information on P2RY1

  • The current model suggests that the released ATP exerts its various influences via a purinergic receptor to regulate outwardly rectifying chloride channels and epithelial sodium channels [7].
  • ATP receptor regulation of adenylate cyclase and protein kinase C activity in cultured renal LLC-PK1 cells [8].
  • P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2 [9].
  • Here we have shown that G(i/o) protein-coupled A1 adenosine receptor (A1R) and Gq protein-coupled P2Y1 receptor (P2Y1R) coimmunoprecipitate in cotransfected HEK293T cells, suggesting the oligomeric association between distinct G protein-coupled P1 and P2 receptors [10].
  • For example, as would be predicted from the beta2 receptor tail mutagenesis studies, NHERF binds to the tail of the purinergic P2Y1 receptor, a seven-transmembrane receptor with an intracellular C-terminal tail ending in D-T-S-L [11].

Chemical compound and disease context of P2RY1

  • 1. The functional activity of deoxyadenosine 5'(alpha-thio)triphosphate (dATP alpha S) was assessed at the cloned human P2Y1 receptor stably expressed in 1321N1 human astrocytoma cells and transiently expressed in Cos-7 cells [12].
  • Incubation of A375 melanoma cells with the P2Y1 receptor-selective agonist 2-methylthioadenosine-5-diphosphate caused a decrease in cell number which was dose-dependent, whereas incubation with the P2Y2 receptor agonist uridine triphosphate caused a dose-dependent increase in cell number [2].
  • The selective P2Y1 receptor antagonist 2'-deoxy-N6-methyl-adenosine-3',5'-diphosphate (MRS2179) and the G(i) protein inhibitor pertussis toxin blocked Ca2+ increase [13].
  • IJP-F was sensitive to the P2Y1 receptor specific antagonist A3P5PS (10muM) and to the G-protein inhibitor, pertussis toxin (PTX, 400ng/ml for 2h) as well as to the small and intermediate Ca(2+) sensitive K(+) channels blocker, apamin (0.3muM) [14].
  • 3'-O-(4-Benzoyl)benzoyl-ATP (BzATP), a photoaffinity analog of ATP, was used as a ligand for a P2Y purinoceptor (adenine nucleotide receptor) present in intact Swiss 3T3 and 3T6 cells and A-431 epidermoid carcinoma cells [15].

Biological context of P2RY1


Anatomical context of P2RY1

  • We have thus cloned a unique member of the P2Y purinoceptor family which probably plays a role in the regulation of cardiac muscle contraction [21].
  • P2Y1 mRNA was only detected in the CALU-3 cell line [22].
  • The P2Y1 and surprisingly the P2Y11 receptors were the most abundantly expressed P2Y receptors in the endothelium [23].
  • We conclude that ADP released from red blood cells enhances PMP formation induced by collagen, and that both P2Y12 and P2Y1 contribute to ADP-potentiation of PMP generation induced by collagen [24].
  • Macrophages and LPS-stimulated monocytes express elevated levels of P2Y1, P2Y2 and P2X7 mRNA, suggesting that both P2Y and P2X receptors can contribute to LPS-induced pathophysiology [25].

Associations of P2RY1 with chemical compounds

  • The potency of nucleotide antagonists at P2Y1 receptors was enhanced by replacing the ribose moiety with a constrained carbocyclic ring (Nandanan, et al. J. Med. Chem. 2000, 43, 829-842) [26].
  • Blockade of ADP receptors, P2Y12 with AR-C69931MX and P2Y1 with A3P5P, respectively, further suppressed collagen-induced PMP formation [24].
  • MRS2365, an (N)-methanocarba analogue of 2-MeSADP, displayed potency (EC50) of 0.4nM at the P2Y1 receptor, with >10000-fold selectivity in comparison to P2Y12 and P2Y13 receptors [27].
  • CD39 (ecto-nucleoside triphosphate diphosphohydrolase-1; E-NTPDase1) is a plasma membrane ecto-enzyme that regulates purinergic receptor signaling by controlling the levels of extracellular nucleotides [28].
  • These results describe specific competitive antagonism of the P2Y1 receptor by an adenine nucleotide derivative and provide a potential new avenue for P2 receptor drug development [1].

Physical interactions of P2RY1

  • Adenosine diphosphate (ADP) initiates and maintains sustained aggregation of platelets through simultaneous activation of both the Gq-coupled P2Y1 receptor and the Gi-coupled P2Y12 receptor [29].
  • The inhibitory effect of preincubation with MRS2365 was circumvented by activation of the Gq-coupled 5-HT2A receptor suggesting that MRS2365 induces loss of the ADP response as a consequence of desensitization of the Gq-coupled P2Y1 receptor [29].
  • We found that TPO did not activate phospholipase C in human platelets and was unable to restore ADP-induced phospholipase C activation upon blockade of the G(q)-coupled P2Y1 receptor [30].
  • The functional properties of the G protein-coupled P2Y1 receptor were investigated in Xenopus oocytes [31].

Regulatory relationships of P2RY1

  • These results further demonstrate the P2Y1 receptor selectivity of MRS2365 and illustrate the occurrence of agonist-induced desensitization of the P2Y1 receptor of human platelets studied in the absence of P2Y12 receptor activation [29].
  • Therefore, CD39 regulates extracellular ATP concentrations and may be an important modulator of purinergic receptor activity in vascular endothelial cells [32].
  • These results suggest that C11 cells express an undetermined type of UTP-sensitive P2-purinoceptors or a unique P2Y-purinoceptor-triggered signaling cascade that leads to inhibition of NKCC1 [33].
  • Activation of P2Y1 receptors on osteoblasts enhances expression of RANKL leading indirectly to an increase in osteoclast formation and resorption [34].

Other interactions of P2RY1

  • No signal was obtained for the P2Y1 and P2Y4 receptors [22].
  • Co-localization of P2Y1 receptor and NTPDase1/CD39 within caveolae in human placenta [35].
  • BACKGROUND: Platelets (PLTs) contain purinergic receptors for ATP (P2X1) and ADP (P2Y1 and P2Y12) that rapidly desensitize upon stimulation with these nucleotides [36].
  • However, ADP-induced activation of integrin alpha(IIb)beta(3) was blocked by antagonists of the G(q)-coupled P2Y1 receptor but was completely restored by the simultaneous co-stimulation of cMpl receptor by TPO [30].
  • Purinergic receptor stimulation has potential therapeutic effects for cystic fibrosis (CF) [37].

Analytical, diagnostic and therapeutic context of P2RY1

  • Using a degenerate PCR approach on MG-63 cell cDNA we found PCR fragments coding for human P2Y1 and a new receptor, P2Y6. cDNA cloning of the P2Y6 receptor identified three cDNA isoforms [38].
  • Overall, Western blotting confirmed the mRNA findings in most aspects, and most interestingly, indicated oligomerization of the P2Y1 receptor that may be important for its function [23].
  • The human P2Y1 purinoceptor has been expressed in Jurkat cells and the effects of HPLC purified nucleotides on calcium movements were measured [39].
  • However, accumulation of GTP-bound Rap1B in platelets activated by co-stimulation of cMpl and P2Y12 receptor was identical to that induced by the simultaneous ligation of P2Y1 and P2Y12 receptor by ADP [30].
  • RT-PCR and immunocytochemistry indicated the additional presence of endogenous P2Y1 and to some extent P2Y4 receptors [40].


  1. Identification of competitive antagonists of the P2Y1 receptor. Boyer, J.L., Romero-Avila, T., Schachter, J.B., Harden, T.K. Mol. Pharmacol. (1996) [Pubmed]
  2. P2Y purinergic receptors regulate the growth of human melanomas. White, N., Ryten, M., Clayton, E., Butler, P., Burnstock, G. Cancer Lett. (2005) [Pubmed]
  3. Pharmacotherapy of the ion transport defect in cystic fibrosis: role of purinergic receptor agonists and other potential therapeutics. Kunzelmann, K., Mall, M. American journal of respiratory medicine : drugs, devices, and other interventions. (2003) [Pubmed]
  4. The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood: involvement of P2Y1 and P2Y12 receptors. Haserück, N., Erl, W., Pandey, D., Tigyi, G., Ohlmann, P., Ravanat, C., Gachet, C., Siess, W. Blood (2004) [Pubmed]
  5. Signaling in human osteoblasts by extracellular nucleotides. Their weak induction of the c-fos proto-oncogene via Ca2+ mobilization is strongly potentiated by a parathyroid hormone/cAMP-dependent protein kinase pathway independently of mitogen-activated protein kinase. Bowler, W.B., Dixon, C.J., Halleux, C., Maier, R., Bilbe, G., Fraser, W.D., Gallagher, J.A., Hipskind, R.A. J. Biol. Chem. (1999) [Pubmed]
  6. Immunohistochemical localization of the P2Y1 purinergic receptor in Alzheimer's disease. Moore, D., Iritani, S., Chambers, J., Emson, P. Neuroreport (2000) [Pubmed]
  7. The cystic fibrosis transmembrane conductance regulator and ATP. Devidas, S., Guggino, W.B. Curr. Opin. Cell Biol. (1997) [Pubmed]
  8. ATP receptor regulation of adenylate cyclase and protein kinase C activity in cultured renal LLC-PK1 cells. Anderson, R.J., Breckon, R., Dixon, B.S. J. Clin. Invest. (1991) [Pubmed]
  9. P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2. Fam, S.R., Paquet, M., Castleberry, A.M., Oller, H., Lee, C.J., Traynelis, S.F., Smith, Y., Yun, C.C., Hall, R.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Heteromeric association creates a P2Y-like adenosine receptor. Yoshioka, K., Saitoh, O., Nakata, H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  11. A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. Hall, R.A., Ostedgaard, L.S., Premont, R.T., Blitzer, J.T., Rahman, N., Welsh, M.J., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  12. An examination of deoxyadenosine 5'(alpha-thio)triphosphate as a ligand to define P2Y receptors and its selectivity as a low potency partial agonist of the P2Y1 receptor. Schachter, J.B., Harden, T.K. Br. J. Pharmacol. (1997) [Pubmed]
  13. Activation of P2Y1 receptor triggers two calcium signaling pathways in bone marrow erythroblasts. Paredes-Gamero, E.J., Craveiro, R.B., Pesquero, J.B., França, J.P., Oshiro, M.E., Ferreira, A.T. Eur. J. Pharmacol. (2006) [Pubmed]
  14. NANC inhibitory neuromuscular transmission in the hamster distal colon. El-Mahmoudy, A., Khalifa, M., Draid, M., Shiina, T., Shimizu, Y., El-Sayed, M., Takewaki, T. Pharmacol. Res. (2006) [Pubmed]
  15. Activation of early events of the mitogenic response by a P2Y purinoceptor with covalently bound 3'-O-(4-benzoyl)-benzoyladenosine 5'-triphosphate. Gonzalez, F.A., Wang, D.J., Huang, N.N., Heppel, L.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  16. Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal keratinocytes. Greig, A.V., Linge, C., Terenghi, G., McGrouther, D.A., Burnstock, G. J. Invest. Dermatol. (2003) [Pubmed]
  17. 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]
  18. 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]
  19. The relative importance of the ADP receptors, P2Y12 and P2Y1, in thrombin-induced platelet activation. Nylander, S., Mattsson, C., Ramström, S., Lindahl, T.L. Thromb. Res. (2003) [Pubmed]
  20. Reciprocal cross-talk between P2Y1 and P2Y12 receptors at the level of calcium signaling in human platelets. Hardy, A.R., Jones, M.L., Mundell, S.J., Poole, A.W. Blood (2004) [Pubmed]
  21. 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]
  22. 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]
  23. P2 receptor expression profiles in human vascular smooth muscle and endothelial cells. Wang, L., Karlsson, L., Moses, S., Hultgårdh-Nilsson, A., Andersson, M., Borna, C., Gudbjartsson, T., Jern, S., Erlinge, D. J. Cardiovasc. Pharmacol. (2002) [Pubmed]
  24. Collagen-induced generation of platelet-derived microparticles in whole blood is dependent on ADP released from red blood cells and calcium ions. Takano, K., Asazuma, N., Satoh, K., Yatomi, Y., Ozaki, Y. Platelets (2004) [Pubmed]
  25. Purinergic receptor regulation of LPS-induced signaling and pathophysiology. Guerra, A.N., Fisette, P.L., Pfeiffer, Z.A., Quinchia-Rios, B.H., Prabhu, U., Aga, M., Denlinger, L.C., Guadarrama, A.G., Abozeid, S., Sommer, J.A., Proctor, R.A., Bertics, P.J. J. Endotoxin Res. (2003) [Pubmed]
  26. Methanocarba modification of uracil and adenine nucleotides: high potency of Northern ring conformation at P2Y1, P2Y2, P2Y4, and P2Y11 but not P2Y6 receptors. Kim, H.S., Ravi, R.G., Marquez, V.E., Maddileti, S., Wihlborg, A.K., Erlinge, D., Malmsjö, M., Boyer, J.L., Harden, T.K., Jacobson, K.A. J. Med. Chem. (2002) [Pubmed]
  27. Agonists and antagonists for P2 receptors. Jacobson, K.A., Costanzi, S., Joshi, B.V., Besada, P., Shin, D.H., Ko, H., Ivanov, A.A., Mamedova, L. Novartis Found. Symp. (2006) [Pubmed]
  28. Cholesterol-dependent lipid assemblies regulate the activity of the ecto-nucleotidase CD39. Papanikolaou, A., Papafotika, A., Murphy, C., Papamarcaki, T., Tsolas, O., Drab, M., Kurzchalia, T.V., Kasper, M., Christoforidis, S. J. Biol. Chem. (2005) [Pubmed]
  29. (N)-methanocarba-2MeSADP (MRS2365) is a subtype-specific agonist that induces rapid desensitization of the P2Y1 receptor of human platelets. Bourdon, D.M., Mahanty, S.K., Jacobson, K.A., Boyer, J.L., Harden, T.K. J. Thromb. Haemost. (2006) [Pubmed]
  30. Thrombopoietin complements G(i)- but not G(q)-dependent pathways for integrin {alpha}(IIb){beta}(3) activation and platelet aggregation. Campus, F., Lova, P., Bertoni, A., Sinigaglia, F., Balduini, C., Torti, M. J. Biol. Chem. (2005) [Pubmed]
  31. A guanine nucleotide-independent inwardly rectifying cation permeability is associated with P2Y1 receptor expression in Xenopus oocytes. O'Grady, S.M., Elmquist, E., Filtz, T.M., Nicholas, R.A., Harden, T.K. J. Biol. Chem. (1996) [Pubmed]
  32. Suppression of ATP diphosphohydrolase/CD39 in human vascular endothelial cells. Imai, M., Kaczmarek, E., Koziak, K., Sévigny, J., Goepfert, C., Guckelberger, O., Csizmadia, E., Schulte Am Esch, J., Robson, S.C. Biochemistry (1999) [Pubmed]
  33. Purinergic-induced signaling in C11-MDCK cells inhibits the secretory Na-K-Cl cotransporter. Brindikova, T.A., Bourcier, N., Torres, B., Pchejetski, D., Gekle, M., Maximov, G.V., Montminy, V., Insel, P.A., Orlov, S.N., Isenring, P. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  34. ATP P2 receptors and regulation of bone effector cells. Gallagher, J.A. Journal of musculoskeletal & neuronal interactions. (2004) [Pubmed]
  35. Co-localization of P2Y1 receptor and NTPDase1/CD39 within caveolae in human placenta. Kittel, A., Csapó, Z.S., Csizmadia, E., Jackson, S.W., Robson, S.C. European journal of histochemistry : EJH. (2004) [Pubmed]
  36. Plasma ectonucleotidases prevent desensitization of purinergic receptors in stored platelets: importance for platelet activity during thrombus formation. Cauwenberghs, S., Feijge, M.A., Hageman, G., Hoylaerts, M., Akkerman, J.W., Curvers, J., Heemskerk, J.W. Transfusion (2006) [Pubmed]
  37. Sustained calcium entry through P2X nucleotide receptor channels in human airway epithelial cells. Zsembery, A., Boyce, A.T., Liang, L., Peti-Peterdi, J., Bell, P.D., Schwiebert, E.M. J. Biol. Chem. (2003) [Pubmed]
  38. 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]
  39. The P2Y1 receptor is an ADP receptor antagonized by ATP and expressed in platelets and megakaryoblastic cells. Léon, C., Hechler, B., Vial, C., Leray, C., Cazenave, J.P., Gachet, C. FEBS Lett. (1997) [Pubmed]
  40. Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293-hP2X3 cells and their inhibition by ethanol and trichloroethanol. Fischer, W., Wirkner, K., Weber, M., Eberts, C., Köles, L., Reinhardt, R., Franke, H., Allgaier, C., Gillen, C., Illes, P. J. Neurochem. (2003) [Pubmed]
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