Techniques for measuring histamine formation in mice

Abstract

1 Formation of ¹⁴C-histamine from ¹⁴C-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 ¹⁴C-histamine in tissues or urine, or inhibiting diamine oxidase and monoamine oxidase and measuring ¹⁴C-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 ¹⁴C-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 ¹⁴C-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 ¹⁴C-histamine in tissues of mice given aminoguanidine and methylhistamine, followed by ¹⁴C-l-histidine. 7 Other approaches listed above may be useful but require improvement, for example, a more specific assay for ¹⁴C-methylhistamine and a stronger, longer-lasting inhibitor of histamine-methylation.