Abstract
General anaesthesia can be induced by a wide variety of structurally dissimilar molecules. Consequently, the mechanism must involve some rather nonspecific interactions at the target site, generally held to be in nerve membranes. The primary site of action has been postulated to be either lipid or protein or both. Although recent work1–4 has cast doubt on the lipid hypotheses, protein models still flourish. In particular, Seeman and his co-workers5–8 have shown that biological membranes expand when anaesthetic molecules are added, and that this expansion is far greater than that which occurs with lipid bilayers. It has been suggested that this difference is due to extensive conformational changes in the membrane proteins, and several mechanisms have been proposed6,9,10 to explain this large expansion of proteins. We now report the first direct measurements of the volumes occupied by general anaesthetic molecules in both biological membranes and lipid bilayers. We show that, in fact, biological membranes expand much less and lipid bilayers expand more than previously reported. The volume that a general anaesthetic molecule occupies is essentially the same in biological membranes, lipid bilayers and water. Our results lead us to question all generalized membrane expansion hypotheses for the mechanism of general anaesthesia, in favour of hypotheses which include more specialized target sites.
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References
Boggs, J. M., Yoong, T. & Hsia, J. C. Molec. Pharmac. 12, 127–135 (1976).
Franks, N. P. & Lieb, W. R. Nature 274, 339–342 (1978).
Franks, N. P. & Lieb, W. R. J. molec. Biol. 133, 469–500 (1979).
Richards, C. D. et al. Nature 276, 775–779 (1978).
Seeman, P., Kwant, W. O. & Sauks, T. Biochim. biophys. Acta 183, 499–511 (1969).
Seeman, P. Pharmac. Rev. 24, 583–655 (1972).
Seeman, P. & Roth, S. Biochim. biophys. Acta 255, 171–177 (1972).
Seeman, P. Experientia 30, 759–760 (1974).
Ueda, I., Kamaya, H. & Eyring, H. Proc. natn. Acad. Sci. U.S.A. 73, 481–485 (1976).
Eyring, H., Woodbury, J. W. & D'Arrigo, J. S. Anesthesiology 38, 415–424 (1973).
Kratky, O., Leopold, H. & Stabinger, H. Meth. Enzym. 27, 98–110 (1973).
Richards, C. D. in Topical Reviews in Anaesthesia Vol. 1 (eds Norman, J. & Whitwam, J. G.) 1–84 (John Wright, Bristol, 1980).
Richards, E. G. An Introduction to Physical Properties of Large Molecules in Solution (Cambridge University Press, 1980).
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).
Melchior, D. L., Scavitto, F. J. & Steim, J. M. Biochemistry 19, 4828–4834 (1980).
Simon, S. A. & Bennett, P. B. in Molecular Mechanisms of Anesthesia Vol. 2 (ed. Fink, B. R.) 305–318 (Raven, New York, 1980).
Pang, K. Y., Braswell, L. M., Chang, L., Sommer, T. J. & Miller, K. W. Molec. Pharmac. 18, 84–90 (1980).
Richards, C. D. Int. Rev. Biochem. 19, 157–220 (1978).
Dodge, J. T., Mitchell, C. & Hanahan, D. J. Archs Biochem. Biophys. 100, 119–130 (1963).
Regan, M. J. & Eger, E. I. Anesthesiology 28, 689–700 (1967).
Snedecor, G. W. & Cochran, W. G. Statistical Methods 6th edn (Iowa State University Press, Ames, 1967).
Cleland, W. W. Adv. Enzym. 29, 1–32 (1967).
Metcalfe, J. C., Seeman, P. & Burgen, A. S. V. Molec. Pharmac. 4, 87–95 (1968).
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Franks, N., Lieb, W. Is membrane expansion relevant to anaesthesia?. Nature 292, 248–251 (1981). https://doi.org/10.1038/292248a0
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DOI: https://doi.org/10.1038/292248a0
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