Some aspects of the normal metabolism of histamine in the rat: written for the Gunning Victoria Jubilee Prize in Materia Medica

Since its discovery the literature on the metabolism of Histamine has expanded continually. It has been investigated and discussed with reference to the part which it plays in physiological and pathological conditions. As the methods of investigation have become more sensitive, so a more detailed picture has been drawn of its functions in the body. As drugs have been discovered which influence its actions in the living animal, so its functions seem to become more complicated and varied. However, in spite of all this investigation the place and mode of origin of the body histamine is still ill-defined, and the factors which control, its release in the normal animal are matters of controversy.The present study is essentially an investigation of the metabolism of histamine in the normal animal. The rat was used throughout these investigations because it was easy to handle and because it was known that its urinary excretion of histamine' was high. A large number of experiments have been performed by other workers on various aspects of the metabolism of histamine in the rat, so that there was already a considerable amount of information on which I could base my experiments.My interest in the possibility that the intestinal flora might play an important par t in the animal's metabolism of histamine was first aroused by reading the papers of Hanke and Koessler on the bacterial production of histamine. Hospital experience had effectively demonstrated the powerful action. of chloramphenicol and the sulphonamides on the intestinal flora, and thence it was a simple step to observe their effects on the urinary histamine excretion in the rat. When the ease with which the rats'urinary histamine could be estimated was realised the possibility of using this experimental method for the investigation of histamine liberators was considered. By this means it was hoped that further observations on the possible origin and mode of release of histamine in normal animals might be made.During the investigation it ha: been necessary to perform several experiments in order to extend and clarify the principal observations. These experiments in themselves might possibly have led to profitable lines of investigation. in order to avoid the inviting enquiries which were raised in these ways, certain principles have been carefully followed. In the first place it as decided that the investigations should be performed in animals which were as nearly normal as possible, in order that any conclusions might be drawn with reference to the normal meta - bolism of histamine. Also it was considered that this approach would provide a firm basis fromwhich any further experiments involving operative techniques or the pathological metabolism of histamine might be conducted. In the second place, the experiments have been performed with theultimate object of applying the results and conclusions from then to human beings. The experimental proceiures therefore have been simple and some emphasisehas been placed on the development of new experimental methods which can be used to investigate histamine metabolism in man