Induction of gastric histamine synthesis by H2-receptor antagonists: potentiation of their antisecretory activity by histidine decarboxylase inhibitors

Agents and Actions
Z HusztiR Frenkl

Abstract

The activation of histamine (HA) formation in rat stomach was measured after repeated administration of histamine H2-receptor antagonists and the potentiation of their antisecretory activity was examined in histidine decarboxylase inhibitor (HDI)-pretreated rats. 40 mg/kg of metiamide, given intraperitoneally (i.p.) 24, 16 and 2 h prior to the examination, produced approximately 50% increase in the amount of 14C-histamine, formed from 14C-histidine in the stomach, and an almost equal enhancement in the gastric histidine decarboxylase (HD) activity. An equal dose of the compound did not influence the endogenous histamine level in the glandular stomach whereas it caused a significant increase in the serum histamine content. By similar treatment, 10 mg/kg of cimetidine enhanced the newly formed histamine in the rat stomach by 57%. The potent HDI, 2-hydroxy-5-carbomethoxy-benzyloxyamine (GYKI-11 121) suppressed the metiamide- and cimetidine-induced increases in histamine synthesis to slightly above or below the control values. In pharmacological studies, the antisecretory activity of histamine H2-receptor blockers could markedly be potentiated by HDI. In GYKI-11 121 and NSD-1055-pretreated rats, the inhibiting potency of metiamide ...Continue Reading

References

Apr 7, 1977·European Journal of Pharmacology·Z HusztiT L Sourkes
Oct 1, 1973·Agents and Actions·J W BlackJ H Wyllie
Jan 1, 1968·Physiological Reviews·G Kahlson, E Rosengren
Mar 1, 1972·Clinica Chimica Acta; International Journal of Clinical Chemistry·M A BeavenZ Horáková
Aug 1, 1969·Biochemical Pharmacology·Y Kobayashi, D V Maudsley
Nov 19, 1965·Science·J E Fischer, S H Snyder
Jun 1, 1967·British Journal of Pharmacology and Chemotherapy·M Johnston, G Kahlson

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