Premium
Further studies on the histidine‐histamine relationship in vivo : effects of endotoxin and of histidine decarboxylase inhibitors
Author(s) -
REILLY MARGARET A.,
SCHAYER R. W.
Publication year - 1968
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1968.tb08484.x
Subject(s) - histidine decarboxylase , histamine , histidine , in vivo , histamine n methyltransferase , carboxy lyases , chemistry , biochemistry , endocrinology , enzyme , medicine , biology , histamine h2 receptor , receptor , antagonist , microbiology and biotechnology
1 . Mice were injected with ( 14 C)‐ l ‐histidine, killed at various intervals, and tissues assayed for ( 14 C)‐histamine. In some cases free ( 14 C)‐ l ‐histidine and total ( 14 C) were also determined. 2 . Removal of stomach, the most active histamine‐forming tissue, failed to reduce the ( 14 C)‐histamine content of any tested tissue; ( 14 C)‐histamine concentrations in lung and muscle of gastrectomized mice were higher than in sham‐operated controls. 3 . In mice pretreated with endotoxin and subsequently injected with ( 14 C)‐ l ‐histidine, the ( 14 C)‐histamine content of liver, lung and muscle was markedly higher than in controls. The increased concentrations of ( 14 C)‐histamine in endotoxin‐pretreated mice seemed to reflect a greater rate of formation; they could be attributed neither to changes in tissue concentration of ( 14 C)‐ l ‐histidine, to increased uptake from other tissues, nor to impaired ability to inactivate histamine. 4 . Results of studies on in vivo effectiveness of several histidine decarboxylase inhibitors are reported. 5 . 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.