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Inhibition of Histamine Synthesis in Brain by α‐Fluoromethylhistidine, a New Irreversible Inhibitor: In Vitro and In Vivo Studies
Author(s) -
Garbarg M.,
Barbin G.,
Rodergas E.,
Schwartz J. C.
Publication year - 1980
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1980.tb07858.x
Subject(s) - histidine decarboxylase , histamine , endocrinology , medicine , in vivo , hypothalamus , cerebral cortex , carboxy lyases , cortex (anatomy) , glutamate decarboxylase , chemistry , histaminergic , biology , enzyme , histidine , biochemistry , neuroscience , microbiology and biotechnology
a‐Fluoromethylhistidine (α‐FMH), a new potent inhibitor of histidine decarboxylase (HD), has been used for in vitro and in vivo studies of brain HD. Following a preincubation with (+)‐α‐FMH, brain HD activity was inhibited in a time‐dependent and concentration‐dependent manner. The enzyme activity was not restored by overnight dialysis against standard buffer. The (–) antimer of α‐FMH was ineffective. When injected intraperitoneally in a single dose of 20 mg/kg, (±)‐α‐FMH induced a complete loss in HD activity in cerebral cortex and hypothalamus as well as in peripheral tissues, such as stomach. At a dosage of 100 mg/kg (±)‐α‐FMH did not alter histamine‐ N ‐methyltransferase, DOPA decarboxylase, and glutamate decarboxylase activities. The maximal decrease of HD activity occurred after 2 h in both cerebral cortex and hypothalamus, but the time course of the recovery of enzyme activity was slower in the cerebral cortex. The enzyme activity reached control value within 3 days in hypothalamus and was not fully restored after 4 days in cerebral cortex. Contrasting with the diminished HD activity, a substantial concentration of histamine remained present in five regions of mouse brain. Thus, α‐FMH is a highly specific irreversible inhibitor of brain HD activity and its efficacy makes it useful to study the physiological role of brain histamine.