The metabolism of ring-labeled histamine.

Previous studies on the fate of histamine in the mammalian organism have shown that the substance can be rapidly inactivated (l), although some free histamine may be excreted in the urine, the amount depending on the species (2). The disruption in v&o of the imidazole ring of histamine has not been established nor has an accounting been made of all administered histamine in terms of known metabolic products. Acetylhistamine and imidazole-4(5)-acetic acid are the only histamine metabolites to have been definitely identified in urine. Acetylhistamine seems to be normally present in the urine of rats and carnivores (2, 3), but, as it can be synthesized by intestinal bacteria from histamine arising from dietary histidine (4), its importance in the inactivation of histamine by the mammalian organism has not been evaluated. Imidazole-4(5)-acetic acid, formed in vitro from histamine via imidazole-4(5)-acetaldehyde by the action of the enzyme histaminase (diamine oxidase) (5), has been isolated from the urine of rats injected intraperitoneally with histamine.’ However, since the quantities of histamine administered were necessarily large, the importance of this route of inactivation under normal conditions is uncertain. The present study utilizes radioactive histamine of high specific activity, permitting observations based on physiological concentrations administered into the blood stream. These experiments take no account of histamine metabolism which normally occurs in the intestine. They are designed to simulate the liberation of histamine by the mammalian organism and to trace the fate from this source only.