The effects of inert gases and other general anaesthetics on the release of acetylcholine from the guinea-pig ileum.

1 The actions of a range of general anaesthetic agents on the rates of release of acetylcholine from the guinea-pig ileum were tested, by means of a superfusion system designed to maintain the tissues under physiological conditions in a high pressure chamber.2 Anaesthetic pressures of nitrous oxide, nitrogen, argon, sulphur hexafluoride and carbon tetrafluoride caused increases in acetylcholine ouput but the concentrations required did not parallel their general anaesthetic potencies. The changes were not altered by the application of a pressure of helium which reverses their general anaesthetic actions in vivo.3 Urethane (50.5 mM and 101 mM, but not 16.8 mM) decreased acetylcholine release rates and this effect was not reversed by helium pressure.4 Octanol (1.0 mM, but not 0.124 mM or 0.496 mM) decreased the acetylcholine output. This action was not reversed by helium pressure. The lack of effect on acetylcholine release from tetrodotoxin-treated tissues suggested that the changes were produced by blockade of action potential conduction.5 Phenobarbitone (0.4 mM but not 0.2 mM) also decreased acetylcholine output. Although the concentrations required were lower than those which have been previously shown to block axonal conduction, no changes were seen in tetrodotoxin-treated tissues. The decreases were less when helium pressure was applied than at atmospheric pressure but full pressure reversal, as occurs in vivo, was not seen.6 The effects on acetylcholine output exerted by the anaesthetics studied did not reflect their general anaesthetic action in the concentrations required, the direction of the changes produced or in the response to helium pressure. They represent specific actions which are likely to contribute to the individual differences which are seen between the physiological actions of the anaesthetics in vivo.