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

Abstract

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.

Disposition of Histamine, Its Metabolites, and pros‐Methylimidazoleacetic Acid in Brain Regions of Rats Chronically Infused with α‐Fluoromethylhistidine

“…With one exception, neither we ( Fig. 1) nor others (Bouclier et al, 1983;Cacabelos et al, 1985Cacabelos et al, , 1987Fukuda et al, 1988;Itowi et al, 1989) depleted >80% of histamine in brain of any species after chronic cx-FMHis. One group (Fukuda et al, 1988) reported 90% depletion but only in cortex of guinea pig.…”

“…1) nor others (Bouclier et al, 1983;Cacabelos et al, 1985Cacabelos et al, , 1987Fukuda et al, 1988;Itowi et al, 1989) depleted >80% of histamine in brain of any species after chronic cx-FMHis. One group (Fukuda et al, 1988) reported 90% depletion but only in cortex of guinea pig. This pool(s) of residual histamine is probably not attributable to mast cells, which, except for thalamus, are nearly absent in rat brain (Hough, 1988).…”