Further observations relating to the physiological activity of adenine compounds

IN a previous paper by one of us (A. N. D.) in collaboration with SzentGy6rgyi [Drury and Szent-Gy6rgyi, 1929] the isolation of a substance from heart muscle which had a definite action upon cardiac rhythm was described in some detail. This substance was finally considered to be muscle adenylic acid owing to its chemical and physiological properties. The study of its physiological action was made much the more simple because adenosine was found to have identical biological activities, for this substance can be readily prepared from yeast nucleic acid, while the natural substance is isolated with difficulty and in small quantity from animal tissues. Most of the observations were therefore made with adenosine, and the natural substance used as a check. The physiological observations in that paper chiefly concerned the action upon the mammalian heart. This was first investigated because the isolation of the substance depended upon an effect which we found in the guinea-pig;-namely the production of heart block upon injection. The influence upon the heart of other animals was followed up in detail and the results given. Some of the experimental effects we witnessed have already been seen in the human subject after injection of adenosine and adenylic acid [Honey, Ritchie and Thompson, 1930; Rothman, 1930]. In addition to the cardiac effects, however, we reported observations which showed that the substances had other very decided actions. The fall of blood-pressure, which could not be ascribed solely to a cardiac action, but also depended upon an arterial dilatation; the arrest of intestinal movements and other effects suggested that the cardiac action was only part of the physiological activity of these substances. This was supported by the fact that we obtained biological evidence of the substance in so many tissues throughout the body that it appeared to be