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Letters to Nature
Nature 327, 623 - 625 (18 June 1987); doi:10.1038/327623a0

Molecular distinction between muscarinic acetylcholine receptor subtypes

Kazuhiko Fukuda, Tai Kubo, Isamu Akiba, Akito Maeda, Masayoshi Mishina & Shosaku Numa

Departments of Medical Chemistry and Molecular Genetics, Kyoto University Faculty of Medicine, Kyoto 606, Japan

The muscarinic acetylcholine receptor (mAChR) mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels, through the action of guanine nucleotide-binding regulatory proteins1–3. Pharmacologically distinguishable forms of the mAChR occur in different tissues and have provisionally been classified into M1 (I), M2 cardiac (II) and M2 glandular (III) subtypes on the basis of their difference in apparent affinity for antagonists4–8. In an attempt to elucidate the molecular basis of the functional heterogeneity of the mAChR, we have cloned and sequenced DNAs complementary to porcine cerebral and cardiac messenger RNAs encoding mAChRs and have thereby deduced the primary structures of the receptor proteins9,10. We report here that the messenger RNA generated by transcription of the cardiac complementary DNA directs the formation of a functional mAChR in Xenopus oocytes and that this mAChR differs from the mAChR formed by expression of the cerebral cDNA9 both in acetylcholine (ACh)-induced response and in antagonist binding properties. Our results provide evidence indicating that the mAChR encoded by the cerebral cDNA (designated as mAChR I) and the mAChR encoded by the cardiac cDNA (mAChR II) are of the M1 (I) and the M2 cardiac (II) subtype, respectively.

  1. 1. Burgen, A. S. V. Trends pharmac. Sci. Suppi 5, 1–3 (1984). 2. Brown, D. Nature 319, 358–359 (1986). 3. Oilman, A. G. Trends Neurosci. 9, 460–463 (1986). 4. Hammer, R., Berrie, C. P., Birdsall, N. J. M., Burgen, A. S. V. & Hulme, E. C. Nature 283, 90–92 (1980). 5. Birdsall, N. J. M. & Hulme, E. C. Trends pharmac. Sci. 4, 459–463 (1983). 6. Hammer, R., Giraldo, E., Schiavi, G. B., Monferini, E. & Ladinsky, H. Life Sci. 38,1653–1662 (1986). 7. Watson, M. et al. Trends pharmac. Sci. Suppl. 7, 46–55 (1986). 8. Birdsall, N. J. M. et al. Biochem. Soc. Symp. 52, 23–32 (1986). 9. Kubo, T. et al. Nature 323, 411–416 (1986). 10. Kubo, T. et al. FEBS Lett. 209, 367–372 (1986). 11. Melton, D. A. et al. Nucleic Acids Res. 12, 7035–7056 (1984). 12. Barish, M. E. / Physiol., Land. 342, 309–325 (1983). 13. Miledi, R. & Parker, I. /. Physiol., Lond. 357, 173–183 (1984). 14. Dascal, N., Gillo, B. & Lass, Y. /. Physiol., Lond. 366, 299–313 (1985). 15. Kusano, K., Miledi, R. & Stinnakre, J. / Physiol., Lond. 328, 143–170 (1982). 16. Dascal, N., Landau, E. M. & Lass, Y. / Physiol, Lond. 352, 551–574 (1984). 17. Berrie, C. P., Birdsall, N. J. M., Burgen, A. S. V. & Hulme, E. C. Br. J. Pharmac. Suppl. 78, P67 (1983). 18. Watson, M., Roeske, W. R. & Yamamura, H. I. /. Pharmac. exp. Ther. 237, 419–428 (1986). 19. Hammer, R., Giachetti, A. Life Sci. 31, 2991–2998 (1982). 20. Schimerlik, M. I., Miller, S., Peterson, G. L., Rosenbaum, L. C. & Tota, M. R. Trends pharmac. Sci. Suppl. 7, 2–7 (1986). 21. Cheng, Y.–C. & Prusoff, W. H. Biochem. Pharmac. 22, 3099–3108 (1973). 22. Sugiyama, H., Hisanaga, Y. & Hirono, C. Brain Res. 338, 346–350 (1985). 23. Konarska, M. M., Padgett, R. A. & Sharp, P. A. Cell 38, 731–736 (1984). 24. Sakmann, B. et al. Nature 318, 538–543 (1985).



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