The effect of some ganglionic stimulants and blocking drugs on acetylcholine release from the mammalian neuromuscular junction

Abstract The effect of nicotine, dimethylphenylpiperazinium (DMPP), hexamethonium and pempidine on release of acetylcholine from the guinea-pig phrenic nerve diaphragm preparation has been investigated. Neither nicotine nor DMPP, 2 × 10−5, modified acetylcholine release from the hemidiaphragms at rest or indirectly stimulated at 50/sec: therefore their neuromuscular blocking action has only a postjunctional origin. Hexamethonium, 4 × 10−4, significantly reduced the output of transmitter from preparations stimulated at 50/sec at 38°. It did not affect the release of acetylcholine from hemidiaphragms at rest or the acetylcholine content of the muscle. The presynaptic effect of hexamethonium is probably related to its linkage with “receptors” present on the surface of the nerve endings. Pempidine, 1 × 10−4, diminished the release of acetylcholine from the preparations at rest or stimulated either at 50 or at 6/sec. The effect was related to the frequency and to the temperature. Moreover, the drug reduced the acetylcholine content of the muscle. This effect may be the result of non-specific metabolic inhibition or of an impairment of choline transport system.