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

From National Research Council Canada

DOI	Resolve DOI: https://doi.org/10.1021/bi00400a003
Author	Search for: Auger, Michèle¹; Search for: Jarrell, Harold C.¹; Search for: Smith, Ian C. P.¹; Search for: Wong, Patrick T. T.¹; Search for: Siminovitch, David (Dave)¹; Search for: Mantsch, Henry H.¹
Affiliation	National Research Council of Canada
Format	Text, Article
Abstract	Because 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	1987-12
In	Biochemistry 26, no. 26: 8513–8516.
Language	English
Peer reviewed	Yes
NRC number	NRCC 28296 AUGER1987
NPARC number	9381215
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Record identifier	e427a7d2-9e9a-472a-a927-ebbec683b93f
Record created	2009-07-10
Record modified	2020-03-17

Date modified:: 2025-11-12