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Molecular Pharmacology, Vol 12, 136-143, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Site and Mechanism of Anesthetic Action

II. Pressure Effect on the Nerve Conduction-Blocking Activity of a Spin Label Anesthetic

J. M. BOGGS 1, S. H. ROTH 1, T. YOONG 1, E. WONG 1, and J. C. HSIA 1

1 Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

A pressure of 100 atm was found to enhance the nerve-blocking activity of a spin label anesthetic, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). This pressure-enhanced nerve conduction block was completely reversible. The mechanism of enhancement was investigated by monitoring the effect of pressure on the resonance spectrum of TEMPO in nerve membranes. Pressure caused only a small decrease in partition coefficient, and no change in binding site was detected. The enhanced activity could not be ascribed to any special property of spin label anesthetics. This finding suggests that the pressure effect on narcosis is not unique. Pressure can enhance, reverse, or have no effect on the anesthetized state. It is argued that different anesthetics may act on different sites which do not respond in the same way to pressure. These diverse effects of pressure on the anesthetized state can be rationalized in terms of anesthetic and pressure effects on membrane proteins.

Submitted on December 16, 1974






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