Abstract
EXTRACELLULAR ATP exerts its effects through P2 purino-ceptors1: these are ligand-gated ion channels (P2x)2,3 or G-protein-coupled receptors (Piv, Piu)4- ATP at P2X receptors mediates synaptic transmission between neurons5–7 and from neurons to smooth muscle1, being responsible, for example, for sympathetic vasoconstriction in small arteries and arterioles8,9. We have now cloned a complementary DNA encoding the P2x receptor from rat vas deferens and expressed it in Xenopus oocytes and mammalian cells. ATP activates a cation-selective ion channel with relatively high calcium permeability. Structural predictions suggest that the protein (399 amino acids long) is mostly extracellular and contains only two transmembrane domains plus a pore-forming motif which resembles that of potassium channels. The P2x receptor thus defines a new family of ligand-gated ion channels.
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References
Burnstock, G. Ann. N. Y. Acad. Sci. 603, 1–17 (1990).
Bean, B. P. Trends pharmac. Sci. 13, 87–90 (1992).
Bean, B. P. & Friel, D. D. Ion Channels 2, 169–203 (1990).
Barnard, E. A., Burnstock, G. & Webb, T. E. Trends pharmac. Sci. 15, 67–71 (1994).
Evans, R. J., Derkach, V. & Surprenant, A. Nature 357, 503–505 (1992).
Edwards, F. A., Gibb, A. J. & Colquhoun, D. Nature 359, 144–147 (1992).
Silinsky, E. M., Gerzanich, V. & Vanner, S. M. Br. J. Pharmac. 106, 762–763 (1994).
Burnstock, G. Trends pharmac. Sci. 9, 116–117 (1988).
Evans, R. J. & Surprenant, A. Br. J. Pharmac. 106, 242–249 (1992).
Benham, C. D. & Tsien, R. W. Nature 328, 275–278 (1987).
Ziganshin, A. U. et al. Br. J. Pharmac. 111, 923–929 (1994).
Abbrachio, M. P. & Burnstock, G. Pharmac. Therap. (in tne press).
Bo, X., Simon, J., Burnstock, G. & Barnard, E. A. J. biol. Chem. 267, 17581–17587 (1992).
Walker, J., Saraste, M., Runswick, M. & Gay, N. EMBO J. 1, 945–951 (1982).
North, R. A. (ed.) Handbook of Receptors and Channels Vol. 2 (CRC Press, Toca Baton, Florida, USA, in the press).
Ashford, M. L. J., Bond, C. T., Blair, T. A. & Adelman, J. P. Nature 370, 456–459 (1994).
Durell, S. R. & Guy, H. R. Biophys. J. 62, 238–250 (1992).
Barnard, E. A. Trends biochem. Sci. 17, 368–374 (1992).
Chalfie, M., Driscoll, M. & Huang, M. Nature 361, 504 (1993).
Canessa, C. M. et al. Nature 367, 463–467 (1994).
Owens, G. P., Hahn, W. E. & Cohen, J. J. Molec. cell. Biol. 11, 4177–4188 (1991).
Zheng, L. M., Zychlinsky, A., Liu, C.-C., Ojcius, D. M. & Young, J. D.-E. J. cell. Biol. 112, 279–288 (1991).
Zoeteweij, J. P., van de Water, B., de Bont, H. J. G. M., Mudler, G. J. & Nagelkerke, J. F. Biochem. J. 288, 207–213 (1992).
Spranzi, E., Djeu, J. Y., Hoffman, S. L., Epling-Burnette, P. K. & Blanchard, D. K. Blood 82, 1578–1585 (1993).
Felgner, P. L. et al. Proc. natn. Acad. Sci. U.S.A. 84, 7413–7417 (1987).
Adams, D. J., Dwyer, T. M. & Hille, B. J. gen. Physiol. 75, 493–510 (1980).
Kubo, Y., Baldwin, T. J., Jan, Y. N. & Jan, L. Y. Nature 362, 127–133 (1993).
Kubo, Y., Reuveny, E., Slesinger, P. A., Jan, Y. N. & Jan, L. Y. Nature 364, 802–806 (1993).
Henikoff, S. Meth. Enzym. 155, 156–165 (1987).
Schaeren-Weimers, N. & Gerfin-Moser, A. Histochemistry 100, 431–440 (1993).
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Valera, S., Hussy, N., Evans, R. et al. A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP. Nature 371, 516–519 (1994). https://doi.org/10.1038/371516a0
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DOI: https://doi.org/10.1038/371516a0
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