Further studies on histamine catabolism in vivo

Abstract

1. Histamine catabolism in vivo was studied in mice and rats; tissues from animals killed 2.5 min after intravenous injection of (14)C-histamine were assayed for (14)C-histamine and total (14)C. Aminoguanidine, a diamine oxidase inhibitor, and methylhistamine, an inhibitor of the histamine methylating enzyme, were used to evaluate the roles of these enzymes in individual tissues.2. Mouse liver and lung appeared to catabolize exogenous histamine rapidly and completely by methylation. In vivo histamine methylating activity was also found in mouse muscle, heart, kidney and lymph node, but not in stomach or intestine.3. In rats (14)C-histamine was inactivated more slowly than in mice. Catabolism was most rapid in intestine where both diamine oxidase and methylating activities were found. Liver had only diamine oxidase activity. Heart showed no catabolism but had extraordinary ability to extract (14)C-histamine from blood.4. The in vivo evaluation of histamine methylation by individual mouse and rat tissues agrees closely with in vitro findings by another laboratory.5. Aminoguanidine reduced uptake of blood (14)C-histamine by some tissues presumably by occupying sites where histamine is normally bound.6. The marked differences between tissues of mice and rats in destroying (14)C-histamine support earlier evidence that there is no apparent relationship between histamine catabolism and function.7. Urine from mice with both major catabolic pathways blocked showed evidence of an abnormal excretory product of (14)C-histamine. Paper chromatograms of urine of male and female mice showed no evidence of a sex difference in catabolism of injected (14)C-histamine.8. A procedure which may permit evaluating contributions of individual tissues to histamine formation in vivo is presented.9. Pretreatment of mice with antihistamines, or with a histamine analogue, betahistine, did not significantly affect the rate of in vivo(14)C-histamine inactivation.