Abstract
Since the first identification of P2Y receptor sequences in 1993, it has quickly become apparent that this family of the G-protein coupled receptors is very diverse. Members of this receptor family are activated extra-cellularly by a wide variety of adenosine and uridine nucleotides including sugar-nucleotides. The recent decipherment of the Human Genome has enabled us to search for new, yet undiscovered P2Y receptor subtypes. In this article we examine the relationships of six orphan G-protein coupled receptor (GPCR) sequences which show considerable sequence homology to various P2Y receptors. The clustering at a few chromosomal loci of P2Y receptor genes and their related orphan genes further suggests that particular P2Y subsets were derived from the same ancestral gene during evolution.
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Abbracchio, M. P., Boeynaems, J. M., Barnard, E. A., Boyer, J. L., Kennedy, C., Miras-Portugal, M. T., King, B. F., Gachet, C., Jacobson, K. A., Weisman G. A., Burnstock, G. (2003) The UDP-glu-cose receptor renamed the P2Y14 receptor. Trends. Pharmacol. Sci. 24, 52–55.
Akbar, G. K. M., 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. (1996) Molecular cloning of a novel P2 purinoceptor from human erythroleukaemic cells. J. Biol. Chem. 271, 18363–18367.
Barnard, E. A. (1992) Receptor classes and the transmitter-gated ion channels. Trends Biochem. Sci. 17, 368–374.
Barnard, E. A. (1992) Classes of receptor subunits, analysis and reconstitution. In: Burgen, A. V., Barnard, E. A., Roberts, G. C. K. (eds) Receptor Subunits and Complexes. Cambridge University Press, pp. 97–117.
Barnard, E. A., Burnstock. G., Webb, T. E. (1994) G-protein-coupled receptors for ATP and other nucleotides: a new receptor family. Trends Pharm. Sci. 15, 67–70.
Barnard, E. A., Simon, J. (2001) An elusive receptor is finally caught: P2Y12, an important drug target in platelets. Trends Pharmacol. Sci. 2, 388–391.
Bean, B. P. (1992) Pharmacology and electrophysiology of ATP-activated ion channels. Trends Pharmacol. Sci. 13, 87–90.
Bogdanov, Y., Dale, L., King, B. F., Whittock, N., Burnstock, G. (1997) Early expression of a novel nucleotide receptor in the neural plate of xenopus embryos. J. Biol. Chem. 272, 12583–12590.
Boyer, J. L., Waldo, G. L., Harden, T. K. (1997) Molecular cloning and expression of an avian G protein-coupled P2Y receptor. Mol. Pharmacol. 52, 928–934.
Brake, A. J., Wagenbach, M. J., Julius, D. (1994) New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature 371, 519–523.
Burnstock, G. (1972) Purinergic nerves. Pharmacol. Rev. 24, 509–581.
Burnstock, G. (1990) Purinergic mechanisms. Ann. N.Y. Acad. Sci 603, 1–17.
Burnstock, G. (1996) Development and perspectives of the purinoceptor concept. J. Auton. Pharmacol. 16, 295–302.
Burnstock, G., Kennedy, C. (1985) Is there a basis for distinguishing two types of P2-purinoceptor? Gen. Pharmacol. 16, 433–440.
Chambers, J. K., Macdonald, L. E., Sarau, H. M., Ames, R. S., Freeman, K., Foley, J. J., Zhu, Y., McLaughlin, M. M., Murdock, P., McMillan, L., Trill, J., Swift, A., Aiyar, N., Taylor, P., Vawter, L., Naheed, S., Szekeres, P., Hervieu, G., Scott, C., Watson, J. M., Murphy, A. J., Duzic, E., Klein, C., Bergsma, D. J., Wilson, S., Livi, G. P. (2000) A G protein-coupled receptor for UDP-glucose. J. Biol. Chem. 275, 10767–10771.
Cheng, A. W., Kong, L. W., Tung, E. K., Siow, N. L., Choi, R. C., Zhu, S. Q., Peng, B. H., Tsim, K. W. (2003) cDNA encodes Xenopus P2Y1 nucleotide receptor: expression at the neuromuscular junctions. Neuroreport 14, 351–357.
Communi, D., Suarez-Gonzalez, N., Detheux, M., Brézillon, S., Vincent-Lannoy, V., Parmentier, M., Boeynaems, J. M. (2001) Identification of a novel human ADP receptor coupled to Gi. J. Biol. Chem. 276, 41479–41485.
Dranoff, J. A., O’Neill, A. F., Franco, A.M., Cai, S.Y., Connolly, G. C., Ballatori, N., Boyer, J. L., Nathanson, M. H. (2000) A primitive ATP receptor from the little skate Raja erinacea. J. Biol. Chem. 275, 30701–30706.
Jacobs, K. A., Collins-Racie, L. A., Colbert, M., Duckett, M., Golden-Fleet, M., Kelleher, K., Kriz, R., LaVallie, E. R., Merberg, D., Spaulding, V., Stover, J., Williamson, M. J., McCoy, J. M. (1997) A genetic selection for isolating cDNAs encoding secreted proteins. Gene 198, 289–296.
King, B. F., Townsend-Nicolson, A. (2000) Recombinant P2Y receptors: the UCL experience. J. Auton. Nerv. Syst. 81, 164–170.
King, B. F., Burnstock, G., Boyer, J. L., Boeynaems, J. M., Weisman, G. A., Kennedy, C., Jacobson, K. A., Humphries, R. G., Abbracchio, M. P., Gachet, C., Miras-Portugal, M. T. (2000) P2Y receptors. IUPHAR Compendium of Receptors Characterization and Classification. IUPHAR Media, London, pp. 307–320.
Lee, D. K., George, S. R., Evans, J. F., Lynch, K. R., O’Dowd, B. F. (2001) Orphan G protein-coupled receptors in the CNS. Curr. Opin. Pharmacol. 1, 31–39.
Lustig, K. D., Shiau, A. K., Brake, A. J., Julius, D. (1993) Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc. Natl. Acad. Sci. USA 90, 5113–5117.
Mellor, E. A., Maekawa, A., Austen, K. F., Boyce, J. A. (2001) Cysteinyl leukotriene receptor 1 is also a pyrimidinergic receptor and is expressed by human mast cells. Proc. Natl. Acad. Sci. USA 98, 7964–7969.
North, R. A., Barnard, E. A. (1997) Nucleotide receptors. Curr. Opin. Neurobiol. 7, 346–357.
Ralevic, V., Burnstock, G. (1998) Receptors for purines and pyrimidines. Pharmacol. Rev. 50, 413–492.
Thompson, J. D., Higgins, D. G., Gibson, T. J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucl. Acids. Res. 22, 4673–4680.
Toguchida, J., McGee, T. L., Paterson, J. C., Eagle, J. R., Tucker, S., Yandell, D. W., Dryja, T. P. (1993) Complete genomic sequence of the human retinoblastoma susceptibility gene. Genomics 17, 535–543.
Valera, S., Hussy, N., Evans, R. J., Adami, N., North, R. A., Surprenant, A., Buell, G. (1994) A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP. Nature 371, 516–519.
von Kugelgen, I., Wetter, A. (2000). Molecular pharmacology of P2Y receptors. Naunyn-Schmiedeberg’s Arch. Pharmacol. 362, 310–323.
Walker, J. E., Saraste, M., Runswick, M. J., Gay, N. J. (1982) Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1, 945–951.
Webb, T. E., Simon, J., Krishek, B. J., Bateson, A. N., Smart, T. G., King, B. F., Burnstock, G., Barnard, E. A. (1993) Cloning and functional expression of a brain G-protein-coupled ATP receptor. FEBS Lett. 324, 219–225.
Webb, T. E., Henderson, D., King, B. F., Wang, S., Simon, J., Bateson, A. N., Burnstock, G., Barnard E. A. (1996) A novel G protein coupled P2 purinoceptor (P2Y3) activated preferentially by nucleo-side diphosphates. Mol. Pharmacol. 50, 258–265.
Webb, T. E., Kaplan, M. G., Barnard, E. A. (1996) Identification of 6H1 as a P2Y purinoceptor: P2Y5. Biochem. Biophys. Res. Commun. 219, 105–110.
Wittenberger, T., Schaller, H. C., Hellebrand, S. (2001) An expressed sequence tag (est) data mining strategy succeeding in the discovery of new G-protein coupled receptors. J. Mol. Biol. 307, 799–813.
Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., Shimizu, T. (1997) A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 387, 620–624.
Zhang, F. L., Luo, L., Gustafson, E., Palmer, K., Qiao, X., Fan, X., Yang, S., Laz, T. M., Bayne, M., Monsma, F. (2002) P2Y13: Identification and characterization of a novel Gi-coupled ADP receptor from human and mouse. J. Pharmacol. Exp. Ther. 301, 705–713.
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This work was supported by the Wellcome Trust.
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Dedicated to Professor Maria Wollemann on the occasion of her 80th birthday.
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Simon, J., Barnard, E.A. The P2Y Nucleotide Receptors in the Human Genome. BIOLOGIA FUTURA 54, 191–201 (2003). https://doi.org/10.1556/ABiol.54.2003.2.8
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DOI: https://doi.org/10.1556/ABiol.54.2003.2.8