Site and mechanism of anesthetic action. II. Pressure effect on the nerve conduction-blocking activity of a spin label anesthetic
Boggs, J.M.; Roth, S.H.; Yoong, T.; Wong, E.; Hsia, J.C.
Molecular Pharmacology 12(1): 136-143
1976
ISSN/ISBN: 0026-895X PMID: 176565 Document Number: 107360
A pressure of 100 atm enhanced 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 (rat phrenic nerve and desheathed frog sciatic nerve). 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, suggesting that the pressure effect on narcosis is not unique. Pressure can enhance, reverse, or have no effect on the anesthetized state. 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.