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Do general anaesthetics act by competitive binding to specific receptors?


Most proteins are insensitive to the presence of anaesthetics at concentrations which induce general anaesthesia, while some are inhibited by certain agents but not others1. Here we show that, over a 100,000-fold range of potencies, the activity of a pure soluble protein (firefly luciferase) can be inhibited by 50% at anaesthetic concentrations which are essentially identical to those which anaesthetize animals. This identity holds for inhalational agents (such as halothane, methoxyflurane and chloroform), aliphatic and aromatic alcohols, ketones, ethers and alkanes. This finding is all the more striking in view of the fact that the inhibition is shown to be competitive in nature, with anaesthetic molecules competing with substrate (luciferin) molecules for binding to the protein. We show that the anaesthetic-binding site can accommodate only one large, but more than one small, anaesthetic molecule. The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors.

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  1. Franks, N. P. & Lieb, W. R. Nature 300, 487–493 (1982).

    Article  ADS  CAS  Google Scholar 

  2. Halsey, M. J. & Smith, E. B. Nature 227, 1363–1365 (1970).

    Article  ADS  CAS  Google Scholar 

  3. White, D. C. & Dundas, C. R. Nature 226, 456–458 (1970).

    Article  ADS  CAS  Google Scholar 

  4. Middleton, A. J. & Smith, E. B. Proc. R. Soc. B193, 159–171 (1976).

    ADS  CAS  Google Scholar 

  5. Middleton, A. J. & Smith, E. B. Proc. R. Soc. B193, 173–190 (1976).

    ADS  CAS  Google Scholar 

  6. Ueda, I. & Kamaya, H. Anesthesiology 38, 425–436 (1973).

    Article  CAS  Google Scholar 

  7. Adey, G., Wardley-Smith, B. & White, D. Life Sci. 17, 1849–1854 (1976).

    Article  Google Scholar 

  8. Branchini, B. R., Marschner, T. M. & Montemurro, A. M. Analyt. Biochem. 104, 386–396 (1980).

    Article  CAS  Google Scholar 

  9. DeLuca, M. & McElroy, W. D. Biochemistry 13, 921–925 (1974).

    Article  CAS  Google Scholar 

  10. Wishnia, A. & Pinder, T. W. Biochemistry 5, 1534–1542 (1966).

    Article  CAS  Google Scholar 

  11. Robillard, K. A. & Wishnia, A. Biochemistry 11, 3835–3840 (1972).

    Article  CAS  Google Scholar 

  12. DeLuca, M. Biochemistry 8, 160–166 (1969).

    Article  CAS  Google Scholar 

  13. Denburg, J. L., Lee, R. T. & McElroy, W. D. Archs Biochem. Biophys. 134, 381–394 (1969).

    Article  CAS  Google Scholar 

  14. Franks, N. P. & Lieb, W. R. Nature 274, 339–342 (1978).

    Article  ADS  CAS  Google Scholar 

  15. Seeman, P. Pharmac. Rev. 24, 583–655 (1972).

    CAS  Google Scholar 

  16. LaBella, F. S. Perspect. Biol. Med. 25, 322–331 (1982).

    Article  CAS  Google Scholar 

  17. Richards, C. D. et al. Nature 276, 775–779 (1978).

    Article  ADS  CAS  Google Scholar 

  18. Steward, A., Allott, P. R., Cowles, A. L. & Mapleson, W. W. Br. J. Anaesth. 45, 282–293 (1973).

    Article  CAS  Google Scholar 

  19. Miller, K. W. & Smith, E. B. in A Guide to Molecular Pharmacology-Toxicology Vol. 1 (ed. Featherstone, R. M.) 427–475 (Dekker, New York, 1973).

    Google Scholar 

  20. Brink, F. & Posternak, J. M. J. cell. comp. Physiol. 32, 211–233 (1948).

    Article  CAS  Google Scholar 

  21. Miller, K. W., Paton, W. D. M., Smith, R. A. & Smith, E. B. Molec. Pharmac. 9, 131–143 (1973).

    CAS  Google Scholar 

  22. Kita, Y., Bennett, L. J. & Miller, K. W. Biochim. biophys. Acta 647, 130–139 (1981).

    Article  CAS  Google Scholar 

  23. Cherkin, A. & Catchpool, J. F. Science 144, 1460–1462 (1964).

    Article  ADS  CAS  Google Scholar 

  24. Abraham, M. H. J. Am. chem. Soc. 104, 2085–2094 (1982).

    Article  CAS  Google Scholar 

  25. Coraish-Bowden, A. Fundamentals of Enzyme Kinetics (Butterworths, London, 1979).

    Google Scholar 

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Franks, N., Lieb, W. Do general anaesthetics act by competitive binding to specific receptors?. Nature 310, 599–601 (1984).

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