[Fatty acid-induced reversal of general anesthesia: chain length-dependence of antagonizing potencies of fatty acids].
Anesthesia is always antagonized by high pressure in the range of 100 atm. The pressure reversal means that the volume of the macromolecule in the anesthetized state is larger than the awake state. Long-chain fatty acids tightened the structure of firefly luciferase whereas anesthetics unfolded the enzyme structure. As expected from these findings, myristate (C 14 fatty acid) at 40 microM increased the EC50 values of volatile anesthetics 250% in goldfish. This study was performed to test the hypothesis that anesthesia antagonism by fatty acid in goldfish was caused by nonspecific action on proteins. We therefore studied the chain length-dependence of the antagonizing potencies of fatty acids. The chain length of 6, 8, 10, 12, and 14 was studied. Ten goldfish were placed in a tub containing 3200 ml distilled water without (control) or with fatty acids. After 30 min of bubbling with halothane vaporized with oxygen into the tub, goldfish were electrically stimulated by constant voltage 20 V for 0.2 sec. Those did not respond to the stimuli were counted as anesthetized. All fatty acids except C 10 increased EC50 of halothane by 50-100% compared to the control (1.13% atm). However, the fatty acid concentrations required for antagonizing halothane increased as the chain length decreased, 300 microM in C 6 30-fold higher than 10 microM in C 14. Because water solubility of short-chain fatty acid is higher than long-chain fatty acid, the antagonizing potencies of fatty acids were thus determined not by their concentrations but by their thermodynamic activities (Ferguson's rule). These results suggest that fatty acid-induced anesthesia antagonism may be caused by physical and nonspecific actions on proteins.
Tatara
Tsuneo
T
Department of Anesthesiology, Kyorin University School of Medicine, Tokyo 181-8611.
Watanabe
Junichi
J
Iwao
Yasuhide
Y
Ueda
Issaku
I
D000768:Anesthesia, General; D000777:Anesthetics / Q000037:antagonists & inhibitors*; D000818:Animals; D005227:Fatty Acids / Q000494:pharmacology*; D006054:Goldfish; D006221:Halothane / Q000037:antagonists & inhibitors
D000777:Anesthetics; D005227:Fatty Acids; D006221:Halothane