Inhibition of histamine synthesis in vitro and in vivo by S-alpha-fluoromethylhistidine.
Biochem Pharmacol
; 33(24): 4003-9, 1984 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-6439218
(S)-alpha-Fluoromethylhistidine (alpha-FMH) is a Kcat or "suicide-substrate" inhibitor of partially purified mammalian histidine decarboxylase; i.e. the agent is converted enzymatically to a more active form which effects a time-dependent, irreversible inhibition. Incubation of a alpha-FMH[4-3H] with enzyme and pyridoxal phosphate resulted in an apparently irreversible labeling of protein, with no demonstratable formation of free-amine product, suggesting a very low to non-existent turnover ratio. alpha-FMH was accumulated in isolated mastocytoma cells and effected a time-dependent inhibition of the conversion histidine[3H]----histamine[3H], the latter product having a markedly different distribution between cells and medium than the pre-existing histamine pool. Inhibition of whole-body histidine decarboxylase activity, as specifically measured by alpha-methylhistidine-14COOH----14CO2, was also time dependent. Concomitant reduction in histamine levels was seen only in the rapidly turning-over pools of stomach and brain. However, over the course of 13 weeks of chronic treatment, depletion of the relatively inert mast-cell histamine pool(s) was seen as well.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Histamina
/
Histidina
/
Metilhistidinas
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Biochem Pharmacol
Año:
1984
Tipo del documento:
Article
Pais de publicación:
Reino Unido