The effects of high pressure helium and nitrogen on the release of acetylcholine from the guinea-pig ileum.

1 The effects of high pressures of helium and of nitrogen on acetylcholine release were tested using the guinea-pig ileum as a model preparation. A superfusion system was designed in which this tissue could be maintained under physiological conditions in a high pressure chamber.2 Helium, at a pressure of 136 atm slightly increased the spontaneous output of acetylcholine but produced no significant changes at 68 atm (136 atm is close to the lethal pressure for small mammals).3 The acetylcholine release evoked by electrical stimulation or by 55 mM potassium was not altered by 136 atm of helium. Effects on tetrodotoxin-treated tissues were not consistent.4 Nitrogen, which in contrast to helium possesses general anaesthetic properties, caused considerable increases in spontaneous and in electrically evoked acetylcholine output at pressures which produce anaesthesia. These increases were not changed when helium was used to increase the total pressure to 136 atm, although this reverses the general anaesthetic actions of nitrogen in vivo.5 The increases in rate of acetylcholine release produced by nitrogen were observed in tetrodotoxintreated tissues and in tissues from reserpine-treated animals. In a calcium-free medium the increases were considerably smaller.6 The conclusions from these results are that while high pressures of helium caused little or no change in acetylcholine release rates, nitrogen produced large changes, which were not due to effects on axonal conduction. The effect of nitrogen is not apparently related to its general anaesthetic actions. Differences such as these in transmitter release would be likely to contribute to the differing physiological effects of these two gases.