Abstract
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.
