Turnover and synthesis of diamine oxidase (DAO) in rat tissues. Studies with heparin and cycloheximide

Abstract

High diamine oxidase (DAO) and histamine activity are present in rat intestine, thymus and adrenals, and a close correlation exists between the two activities in these tissues ( Biochem. Pharmac. 24, 979 (1975)). The distribution of histaminase in normal and germ-free rat tissues and the release of this enzyme from intestine, thymus and adrenals was investigated in further detail with a tritium-release assay. Contrary to previous reports, histaminase activity was detected in brian, in the hypothalamus, thalamus and medulla but not in cortex and cerebellum. The enzyme was released by heparin into blood from intestine and adrenals but not from thymus. In high doses, heparin produced almost complete (>80 per cent) depletion of the enzyme in intestine within 1 hr. The enzyme activity reappeared and returned to normal levels by 24 hr. Prior administration of cycloheximide prevented the repletion of enzyme activity. The time course of the responses to the drugs suggested that DAO is synthesized continuously at a relatively rapid rate ( t 1 2 ∼ 10 hr ). Studies in vitro indicated that DAO unlike monoamine oxidase diffuses from the mucosal surface into the lumen of the gut. DAO may therefore have a role in deaminating diamines of bacterial origin in the intestinal contents.