Author

Peter Cokic

Publication Date

1981

Document Type

Dissertation/Thesis

First Advisor

Vanderkooi, Garret

Degree Name

M.S. (Master of Science)

Department

Department of Chemistry

LCSH

Anesthetics--Physiological effect||Microsomes||Cytochrome b₅||Enzymes||Local anesthesia

Abstract

In the course of this work, the effects of local anesthetics were studied on the microsomal NADH-Fe(CN)₆³⁻ oxidoreductase and NADH-cytochrome c oxidoreductase activities as functions of both temperature and anesthetic concentration. The anesthetic agents used were tetracaine, procaine, dibucaine, n-butanol, n-pentanol, and benzyl alcohol. It was observed for both the intact microsomes and the water soluble lipid-free cytochrome b₅ reductase headgroups that the NADH-Fe(CN)₆³⁻ oxidoreductase activity decreased as a function of increasing anesthetic concentration at 30°C. The NADH-cytochrome c oxidoreductase activity was stimulated at low anesthetic concentrations, but was inhibited at higher concentrations at the same temperature. Since NADH-Fe(CN)₆³⁻ oxidoreductase activity depends on the presence of only membrane bound cytochrome b₅ reductase, the inhibition of this enzyme activity may be attributed to an anesthetic protein interaction and does not require the presence of the microsomal lipid bilayer. Because the NADH-cytochrome c oxidoreductase activity depends on lateral diffusion between cytochrome b₅ reductase and cytochrome b₅, the activation at low concentrations may be attributed to the fluidization of the lipid bilayer, induced by an anesthetic lipid interaction. The inhibition of this enzyme activity at higher concentrations may be attributed to an anesthetic protein interaction. It was also observed that a linear correlation existed between the inhibitory potencies of the anesthetic agents required for 50% inhibition and their oil/water partition coefficients. This suggests that hydrophobic interactions may be of importance in the inhibitory reactions.

Comments

Includes bibliographical references.

Extent

v, 70 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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