In vivo studies on histamine catabolism and its inhibition.
1. Histamine catabolism in vivo was studied in mice subjected to various forms of pretreatment; tissues from mice killed 2.5 min after intravenous injection of (14)C-histamine were assayed for (14)C-histamine, (14)C-methylhistamine and total (14)C.2. Pretreatment of mice with aminoguanidine, an inhibitor of diamine oxidase, strongly increased levels of (14)C-histamine in intestine; pretreatment with aminoguanidine plus a monoamine oxidase inhibitor strongly increased levels of (14)C-methylhistamine in liver. Effects in other tissues are reported and discussed.3. Pretreatment of mice with non-isotopic methylhistamine increased levels of (14)C-histamine in liver. Methylhistamine is the first known inhibitor of histamine-methylation in vivo.4. Pretreatment of mice with inhibitors of protein synthesis, drugs which reduce the basal activity of histidine decarboxylase and which block its activation, failed to affect histamine catabolism.5. Pretreatment of mice with endotoxin or with Freund's adjuvant, irritants known to cause activation of histidine decarboxylase, failed to affect histamine catabolism.6. There was no evidence of parallelism between the histamine-destroying enzymes and the histamine-forming enzyme, histidine decarboxylase, either in distribution or ability to undergo changes in activity. No support was obtained for the view that histamine-catabolizing enzymes play a role in the local control of responses to newly formed histamine.
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors; D000818:Animals; D002247:Carbon Isotopes; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006632:Histamine / Q000032:analysis / Q000378:metabolism*; D007275:Injections, Intravenous; D007422:Intestines / Q000032:analysis / Q000201:enzymology; D008099:Liver / Q000032:analysis / Q000201:enzymology; D008745:Methylation; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology
D002247:Carbon Isotopes; D004731:Endotoxins; D006146:Guanidines; D008996:Monoamine Oxidase Inhibitors; D003609:Dactinomycin; D011691:Puromycin; D006632:Histamine; D005620:Freund's Adjuvant; D003513:Cycloheximide; D006631:Amine Oxidase (Copper-Containing); D002262:Carboxy-Lyases