INHIBITION OF THE RELEASE OF ACETYLCHOLINE FROM ISOLATED GUINEA-PIG ILEUM BY CRYSTALLINE TETRODOTOXIN

¹ Departmentof Pharmacology and Toxicology, Institute of Food Microbiology, Chiba University, Okubo, Narashino, Chiba, Japan

In the experiments with the transmurally stimulated guinea-pig ileum, tetrodotoxin in the concentration of more than 30 ng/ml abolished the responses to transmural stimulation, abolished the contractile response to nicotine, reduced the response to 5-hydroxytryptamine and failed to affect response to acetylcholine and histamine. The effects of tetrodotoxin in this preparation were similar to those of cocaine, procaine and morphine, although some points of difference were observed. Hexamethonium had no effect at all on the response to transmural stimulation, although the response to nicotine was blocked. In separate experiments, as little as 1 ng/ml of tetrodotoxin produced a significant reduction of the release of acetylcholine into the bath fluid, but a complete inhibition of the release of acetylcholine was not observed with a 1000-fold increase in the concentration of tetrodotoxin. Tetrodotoxin also had no significant effect on the stretch-induced release of acetylcholine in the guinea-pig ileum. Tetrodotoxin, even in very high concentrations, failed to produce a change in the spontaneous spike discharge in the isolated guinea-pig taenia coli. It was concluded that tetrodotoxin apparently reduced the excitability of post ganglionic cholinergic nerve fibers and thereby permitted the release of acetylcholine from nerve endings during the process of excitation, although it had no effect on the release of acetylcholine from muscular sites.