Abstract
1. Histamine catabolism in vivo was studied in mice and rats; tissues from animals killed 2·5 min after intravenous injection of 14C-histamine were assayed for 14C-histamine and total 14C. 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 14C-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 14C-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 14C-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 14C-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 14C-histamine. Paper chromatograms of urine of male and female mice showed no evidence of a sex difference in catabolism of injected 14C-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 14C-histamine inactivation.
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Selected References
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