Effect of glucocorticoids on histamine metabolism in mice.

1. Histamine formation and catabolism were studied in vivo in standardized experiments; for the former, animals pretreated with inhibitors of histamine catabolism were killed 10 min after intravenous injection of (14)C-L-histidine; for the latter, no inhibitors were used and animals were killed 2.5 min after intravenous injection of (14)C-histamine. In vitro assays of histidine decarboxylase activity were also made.2. Pretreatment of adrenalectomized mice with cortisol for one day caused a major alteration in histamine formation; stomach and intestine were abnormally high in the (14)C-histamine:total (14)C ratio, while most other tested tissues were lower. Brain and thymus were unaffected. Cortisol treatment caused a marked increase in urinary excretion of both (14)C-histamine and total (14)C.3. Following injection of a rapidly absorbed corticoid, significant effects on urine and stomach were demonstrable at 30 min and 4 h, respectively.4. In cortisol-treated adrenalectomized mice histidine decarboxylase activity, relative to controls, was decreased in lung but virtually unaffected in kidney, heart, muscle and liver. In stomach, activity was increased but the statistical significance was low.5. In mice injected with (14)C-histamine, cortisol pretreatment caused a small drop in tissue levels of (14)C-histamine, (14)-methylhistamine and total (14)C, but increased levels in urine. In all cases, however, the ratio of the two amines to total (14)C was not significantly different from controls.6. From the foregoing experiments it was concluded that the results in (2) could be largely attributed to entry into urine of (14)C-histamine and total (14)C, thus reducing the availability of these substances in blood for extraction by tissues. In stomach, the cortisol-induced increase in histamine formation may involve some process other than increased histidine decarboxylase activity.7. The activation of histidine decarboxylase in liver and lung of intact mice by Freund's adjuvant, or by endotoxin, was reduced by corticoid treatment.8. In a single short experiment on the effect of cortisol on histamine formation in adrenalectomized rats, results from stomach, lung and heart, the only tissues assayed, were similar to those from the mouse experiment.