Abstract
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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References
Franks, N. P. & Lieb, W. R. Nature 300, 487–493 (1982).
Halsey, M. J. & Smith, E. B. Nature 227, 1363–1365 (1970).
White, D. C. & Dundas, C. R. Nature 226, 456–458 (1970).
Middleton, A. J. & Smith, E. B. Proc. R. Soc. B193, 159–171 (1976).
Middleton, A. J. & Smith, E. B. Proc. R. Soc. B193, 173–190 (1976).
Ueda, I. & Kamaya, H. Anesthesiology 38, 425–436 (1973).
Adey, G., Wardley-Smith, B. & White, D. Life Sci. 17, 1849–1854 (1976).
Branchini, B. R., Marschner, T. M. & Montemurro, A. M. Analyt. Biochem. 104, 386–396 (1980).
DeLuca, M. & McElroy, W. D. Biochemistry 13, 921–925 (1974).
Wishnia, A. & Pinder, T. W. Biochemistry 5, 1534–1542 (1966).
Robillard, K. A. & Wishnia, A. Biochemistry 11, 3835–3840 (1972).
DeLuca, M. Biochemistry 8, 160–166 (1969).
Denburg, J. L., Lee, R. T. & McElroy, W. D. Archs Biochem. Biophys. 134, 381–394 (1969).
Franks, N. P. & Lieb, W. R. Nature 274, 339–342 (1978).
Seeman, P. Pharmac. Rev. 24, 583–655 (1972).
LaBella, F. S. Perspect. Biol. Med. 25, 322–331 (1982).
Richards, C. D. et al. Nature 276, 775–779 (1978).
Steward, A., Allott, P. R., Cowles, A. L. & Mapleson, W. W. Br. J. Anaesth. 45, 282–293 (1973).
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).
Brink, F. & Posternak, J. M. J. cell. comp. Physiol. 32, 211–233 (1948).
Miller, K. W., Paton, W. D. M., Smith, R. A. & Smith, E. B. Molec. Pharmac. 9, 131–143 (1973).
Kita, Y., Bennett, L. J. & Miller, K. W. Biochim. biophys. Acta 647, 130–139 (1981).
Cherkin, A. & Catchpool, J. F. Science 144, 1460–1462 (1964).
Abraham, M. H. J. Am. chem. Soc. 104, 2085–2094 (1982).
Coraish-Bowden, A. Fundamentals of Enzyme Kinetics (Butterworths, London, 1979).
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Franks, N., Lieb, W. Do general anaesthetics act by competitive binding to specific receptors?. Nature 310, 599–601 (1984). https://doi.org/10.1038/310599a0
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DOI: https://doi.org/10.1038/310599a0
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