STUDIES ON THE HISTIDINE‐HISTAMINE RELATIONSHIP IN VIVO

1972

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Summary1. 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 "C-L-histidine; for the latter, no inhibitors were used and animals were killed 2 5 min after intravenous injection of "IC-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 "IC-histamine: total "IC ratio, while most other tested tissues were lower. Brain and thymus were unaffected. Cortisol treatment caused a marked increase in urinary excretion of both "C-histamine and total "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 "C-histamine, cortisol pretreatment caused a small drop in tissue levels of "C-histamine, "C-methylhistamine and total "IC, but increased levels in urine. In all cases, however, the ratio of the two amines to total "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 "C-histamine and total '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 slimilar to those from the mouse experiment.

Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

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Effect of glucocorticoids on histamine metabolism in mice

1972

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“…In Experiment 3 normal mice, or endotoxin-pretreated mice, were injected intravenously with ("C)-histamine, killed 4 min later, and tissues assayed for total (`C) and ("C)-histamine. This experiment is based on evidence (Schayer, 1953;Reilly and Schayer, 1968) which suggests that within a few minutes after intravenous injection of ("C)-histamine, the ratio of total ("C) to ("C)-histamine in a tissue provides a rough measure of the in vivo histamine-inactivating power of that tissue. Experimental details and results are shown in Table 3.…”

Section: Resultsmentioning

confidence: 99%

Further studies on the histidine‐histamine relationship in vivo: effects of endotoxin and of histidine decarboxylase inhibitors

1968

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. Mice were injected with (14C)‐l‐histidine, killed at various intervals, and tissues assayed for (14C)‐histamine. In some cases free (14C)‐l‐histidine and total (14C) were also determined. . Removal of stomach, the most active histamine‐forming tissue, failed to reduce the (14C)‐histamine content of any tested tissue; (14C)‐histamine concentrations in lung and muscle of gastrectomized mice were higher than in sham‐operated controls. . In mice pretreated with endotoxin and subsequently injected with (14C)‐l‐histidine, the (14C)‐histamine content of liver, lung and muscle was markedly higher than in controls. The increased concentrations of (14C)‐histamine in endotoxin‐pretreated mice seemed to reflect a greater rate of formation; they could be attributed neither to changes in tissue concentration of (14C)‐l‐histidine, to increased uptake from other tissues, nor to impaired ability to inactivate histamine. . Results of studies on in vivo effectiveness of several histidine decarboxylase inhibitors are reported. . The following conclusions are supported by the evidence presented: (a) in stressed mice, those tissues which show activation of histidine decarboxylase also show increased ability to form histamine in vivo; (b) tissue histamine is largely formed locally; (c) histidine decarboxylase inhibitors are highly effective in blocking histamine formation in mast cells and in stomach, but do not normally reach the locus of an inducible form of histidine decarboxylase; (d) the inducible form of histidine decarboxylase in liver may be located in phagocytic microvascular endothelial cells; (e) in conditions favouring near‐maximal activation of histidine decarboxylase, the histamine‐methylating enzyme of liver and diamine oxidase of intestine showed no inducible characteristics; (f) blood histamine concentrations do not accurately reflect changes in tissue histamine formation.

“…A minimum of 4,000 counts was obtained for all samples and background. Full details of our methods have been published (Reilly & Schayer, 1968a.…”

Section: Methodsmentioning

confidence: 99%

Techniques for measuring histamine formation in mice

1971

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Summary1. Formation of "IC-histamine from "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 hist;amine-methylating enzyme, respectively. 2. Four general approaches were used: inhibiting diamine oxidase and the histamine-methylating enzyme and measuring "C-histamine in tissues or urine, or inhibiting diamine oxidase and monoamine oxidase and measuring "ICmethylhistamine 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 "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 "IC-histamine were tested in mice with or without inhilbitors of histamine catabolism. Results were essentially parallel in both cases but higher in the former.6. The method of choice is measurement of "C-histamine in tissues of mice given aminoguanidine and methylhistamine, followed by "C-L-histidine.7. Other approaches listed above may be useful but require improvement, for example, a more specific assay for "IC-methylhistamine and a stronger, longer-lasting inhibitor of histamine-methylation.