Open AccessPartitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia.
Author(s) -
Nicholas P. Franks,
W. R. Lieb
Publication year - 1986
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.83.14.5116
Subject(s) - lipid bilayer , bilayer , chemistry , anesthetic , membrane , partition coefficient , biological membrane , biophysics , cutoff , biological activity , biochemistry , chromatography , biology , in vitro , anesthesia , medicine , physics , quantum mechanics
Alcohols act as anesthetics only up to a certain chain length, beyond which their biological activity disappears. Although the molecular nature of general anesthetic target sites remains unknown, presently available data support the hypothesis that this "cutoff" in anesthetic activity could be due to a corresponding cutoff in the absorption of long-chain alcohols into lipid-bilayer portions of nerve membranes. To test this hypothesis, we have developed an extremely sensitive biological assay, based on inhibition of the light-emitting firefly luciferase reaction, which is capable of measuring lipid-bilayer/buffer partition coefficients K for very lipid soluble compounds. Contrary to the hypothesis and reported data, we find a strictly linear increase in log(K) as the chain length increases [delta(delta G0)CH2 = - 3.63 kJ/mol] for the primary alcohols from decanol to pentadecanol, with no hint of a cutoff. The fact that alcohols continue to partition into lipid bilayers long after their biological activity has ceased is consistent with the view that the primary target sites in general anesthesia are proteins rather than the lipid-bilayer portions of nerve membranes.