| Summary: | In the introduction a brief historical review is given of the importance of histamine as the agent responsible for the development of the signs and symptoms of anaphylactic shock in several animal species. Various aspects of histamine metabolism are considered, including the origin, the intracellular distribution and the rate of detoxication of this substance by histaminase in normal and sensitive individuals, and the kinetics of its release during shock. A possible connection is suggested between the metabolic function of mitochondria and protein metabolism on the one hand and the metabolism of histamine on the other. This scheme is correlated with the ability of intracellular particles to synthesize high energy phosphate bonds. In the experimental section it is shown that histamine-liberating drugs can release histamine from tissue homogenates, but that this action cannot be associated with changes in the activity of intracellular proteolytic enzymes. Evidence is given that three powerful histamine liberators react v/ith adenosine triphosphate and several other phosphates at extremely low concentrations, and that intravenous ATP can modify, or even annul the action of these drugs in the intact animal. A mechanism of histamine release depending on the metabolic activity of the mitochondria is suggested in the discussion. This attempts to explain the explosive nature of histamine release both during anaphylaxis and during the action of the liberating drugs. It also offers a possible explanation for the appearance of smooth muscle stimulating polypeptides.
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