Urinary metabolites of radioactive histamine.

This laboratory has previously shown that, when animals are injected with microgram amounts of high specific activity C4-histamine, at least three radioactive metabolic products can be demonstrated in the urine. Paper chromatograms of the urine in butanol80, ethanol 10, and ammonia 30 showed three radioactive peaks. The following information regarding their identity has been published. Peak 1 is a compound formed by the action of diamine oxidase (l-3). It is not free imidazoleacetic acid (ImAA) although the latter is an intermediate in its formation (4, 5). The occurrence of Peak 1 is blocked by aminoguanidine and other diamine oxidase inhibitors. Peak 2 is a compound formed by the action of an unidentified enzyme system which we have tentatively called “histamine-metabolizing enzyme II” (2). It is not affected by diamine oxidase inhibitors but its formation is almost completely blocked by Marsilid (1-isopropyl-2-isonicotinylhydrazine) and IBINH (I-isobutyl-2-isonicotinylhydrazine) (6). Peak 3 contains unchanged histamine and a small amount of acetyl histamine (4). This paper describes the isolation of two radioactive compounds from the urine of mice given large doses of radioactive histamine of low specific activity. One is a conjugate of ImAA with ribose (7, 8). We have now shown this to be identical with the compound of Peak 1. The second compound, although not fully identified, appears to be a methylated ImAA. This suggested that methylation of the imidazole ring is the first step in the unknown pathway of histamine metabolism attributed to “histaminemetabolizing enzyme II.” Confirmation of this hypothesis has been made, and details will be published separately.