THE intense activity of acetylcholine has been well known since its first description by Hunt and Taveau [1906]. Dale [1914] emphasized the extraordinary evanescence of the effect, when the substance is injected into the blood stream, and suggested that it was probably due to hydrolysis into choline and acetic acid by an esterase in the blood. Loewi and his co-workers [1926], in studying the properties of the substance liberated in the frog's heart by stimulation of the vagus, found that this had the properties of a choline ester, and demonstrated the presence in the heart of an esterase, which destroyed the vagus substance or acetylcholine. In either case the destructive action was inhibited by eserine or ergotamine. Galehr and Plattner [1928] made a detailed study of the effect upon acetylcholine of mammalian blood in vitro. They found that it was, indeed, hydrolysed with extraordinary rapidity. The hydrolytic agent, however, possessed properties which they regarded as incompatible with its being an esteraso. Thus the activity of the blood serum resisted heating to 580 C. and exposure to ultra-violet light. Since they further observed that the destructive activity was concentrated in the corpuscles, so that a suspension of these acted more rapidly than the serum, they concluded that the destructive activity of blood on acetylcholine was due to a surface catalysis, and not to the action of a true ferment. After my own investigations, here recorded, had been largely completed, I was informed, through the courtesy of Prof. 0. Loewi, of an investigation which had been made independently in his laboratory by Dr Engelhardt, and which has since been published [Engelhardt and Lo ewi, 1930], covering to some extent the same ground as my own. Engelhardt and Loewi were able to show that the resistance of the hydrolytic agent to heat and to irradiation is due to the presence of protective substances, the esterase from frog's heart being similarly protected when added to mammalian serum. They also observed the remarkably potent inhibition of the hydrolytic action produced by adding eserine to the blood or serum, even in very low concentrations,
Amatoxins were detected radioimmunologically as early as 90-120 min after ingestion in the gastric fluid and urine of a 15-year-old boy who tried to commit suicide by ingestion of wild mushrooms. This early detection of amatoxins in the urine is proof of rapid absorption from the intestinal tract and subsequent excretion by the kidneys in man.
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