Pressure-induced exclusion of a local anesthetic from model and nerve membranes

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DOIResolve DOI: http://doi.org/10.1021/bi00400a003
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TypeArticle
Journal titleBiochemistry
ISSN0006-2960
1520-4995
Volume26
Issue26
Pages85138516
AbstractBecause it is well established that the anesthetic state can be reversed by pressure, a number of molecular theories that have been proposed for the mechanism of action of both local and general anesthetics can be tested by varying the pressure. Using Fourier transform infrared spectroscopy, we report here the first direct observation of the expulsion from lipid bilayers of a local anesthetic, tetracaine, by pressure. Moreover, we establish for the first time that this phenomenon is common to both model membranes and to myelinated and unmyelinated nerve membranes, vindicating the utility of model membrane systems. A distinctive feature of this behavior in model systems is that, in saturated phosphatidylcholines at high pH, expulsion only occurs in the presence of cholesterol, whose ordering effect on the acyl chains evidently assists pressure in squeezing the anesthetic out of the bilayer. This pressure-induced phenomenon may provide insight into the molecular mechanisms underlying the antagonistic effect of pressure against anesthesia.
Publication date
PublisherAmerican Chemical Society
LanguageEnglish
AffiliationNational Research Council Canada
Peer reviewedYes
NRC number28296
AUGER1987
NPARC number9381215
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Record identifiere427a7d2-9e9a-472a-a927-ebbec683b93f
Record created2009-07-10
Record modified2017-03-14
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