METABOLISM OF ¹⁴C-HISTAMINE IN BRAIN

¹ Research Center, Rockland State Hospital, Orangeburg, New York

1) To test identity of histamine-catabolizing enzymes in mouse brain in vivo, aminoguanidine or methylhistamine, inhibitors of diamine oxidase and the histamine-methylating enzyme, respectively, were injected intracerebrally followed in 25 minutes by ¹⁴C-histamine intracerebrally. After sacrifice 30 minutes later, evidence was found for methylation only. 2) ¹⁴C-histamine, formed in brain after intracerebral injection of ¹⁴C-L-histidine, was also methylated. 3) Amodiaquine, a powerful inhibitor of histamine methylation in vitro, was found to inhibit in vivo. 4) In vitro methylation of ¹⁴C-histamine was tested on brain regions of several species: activities in mice and guinea pigs were of approximately the same magnitude, but those in rats were lower. 5) Only the specific histidine decarboxylase was found in guinea-pig brain: its relative distribution in the major regions was similar to that of mice and rats except for higher activities in cerebellum. 6) Comparison of relative activities of histidine decarboxylase and the histamine-methylating enzyme from brains of three species showed evidence of a rough proportionality between histamine formation and destruction within each major region. This is a unique finding for mammalian tissues and is consistent with a specific role for histamine in brain.