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Long-term depletion of histamine in guinea-pigs by administration of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase; effect on the sensitivity of histamine receptors



Long-term depletion of histamine in guinea-pigs by administration of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase; effect on the sensitivity of histamine receptors



Agents and Actions 24(1-2): 56-64



The effect of intraperitoneal administration of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, at a dose of 100 mg/kg twice a day for 6 weeks on the sensitivity of histamine receptors in the guinea-pigs was examined. The histamine contents in the ileum, heart and brain after the treatment decreased to about 54%, 83% and 9-62% (depending on the region), respectively, of those of controls. However, there were no significant difference in the histamine-induced contraction of the ileum and atrium, the maximal binding (Bmax) and the dissociation constant (Kd) of [3H]-mepyramine binding to membrane fractions of the ileum and brain (except the cortex) and the increase of cyclic AMP formation induced by histamine in membranes of the heart and brain (except the cortex) between alpha-FMH-treated- and untreated animals. These results suggest that long-term histamine depletion dose not significantly affect the sensitivity of histamine receptors of guinea-pig except in the brain cortex.

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Accession: 040596592

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PMID: 3136625


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