Putrescine metabolism and the study of diamine oxidase activity in vivo

Abstract

The catabolism of 14C-putrescine (1,4-tetramethylene-diamine) to labeled CO2 in small laboratory animals has been studied extensively in order to establish the influence of nutritional, endocrine and other factors on this process. Special attention has been paid to treatments that are known to affect the activity of diamine oxidase (DAO, histaminase, EC, 1.4.3.6), a copper-containing enzyme characteristically inhibited by semicarbazide. Thus, copper-deficient rats metabolize putrescine more slowly than their controls. Antimalarial drugs that inhibit histamine N-methyltransferase also inhibit putrescine catabolism in vivo and DAO activity in vitro. Adrenalectomized rats metabolize the diamine at a reduced rate, a result consistent with the previously demonstrated decrease of DAO in the tissues of several species of animal. There is no effect on the rate of catabolism of putrescine when thyroid state is altered. Heparin (up to 15,000 U/kg), which releases DAO from the small (0.1 mg/kg), intestine, and aminoguanidine (0.1 mg/kg), which inhibits the enzyme powerfully, both cause decreased rates of catabolism of the diamine in rats. The putrescine-catabolizing ability returns with a half-time of recovery of 15-18 h, corresponding to the estimates of SHAFF and BEAVEN [36] for recovery of intestinal DAO activity following administration of heparin or cycloheximide. Together with out other results this suggests that what is being measured by putrescine catabolism depends to a significant extent on the activity of DAO in vitro.