Techniques for measuring histamine formation in mice

1. Formation of (14)C-histamine from (14)C-L-histidine was studied in mice using various inhibitors of histamine catabolism; these included aminoguanidine, pargyline and methylhistamine, inhibitors of diamine oxidase, monoamine oxidase, and the histamine-methylating enzyme, respectively.2. Four general approaches were used: inhibiting diamine oxidase and the histamine-methylating enzyme and measuring (14)C-histamine in tissues or urine, or inhibiting diamine oxidase and monoamine oxidase and measuring (14)C-methylhistamine in tissues or urine. In some tests mice with normal concentrations of histidine decarboxylase were used; in others the enzyme was activated by pretreating mice with Freund's adjuvant.3. Methylhistamine pretreatment increased (14)C-histamine in several tissues of mice but aminoguanidine had no significant effect; it was concluded that endogenously formed histamine is inactivated almost entirely by methylation.4. There was no evidence of parallelism between the ability of tissues to form histamine and to inactivate endogenous histamine.5. Effects of Freund's adjuvant on tissue concentrations of (14)C-histamine were tested in mice with or without inhibitors of histamine catabolism. Results were essentially parallel in both cases but higher in the former.6. The method of choice is measurement of (14)C-histamine in tissues of mice given aminoguanidine and methylhistamine, followed by (14)C-L-histidine.7. Other approaches listed above may be useful but require improvement, for example, a more specific assay for (14)C-methylhistamine and a stronger, longer-lasting inhibitor of histamine-methylation.