Suppression of rat stomach histidine decarboxylase activity by histamine: H2‐receptor‐mediated feed‐back

Abstract

Gastrin activates rat stomach histidine decarboxylase. Exogenous histamine suppressed basal enzyme activity in unoperated, in nephrectomized, in vagally denervated and in antrectomized rats and counteracted the pentagastrin-induced enzyme activation in unoperated rats. Kinetic analysis of enzyme-catalyzed histidine decarboxylation in extracts from untreated vagotomized and from histamine-treated vagotomized rats showed that histamine-induced suppression of histidine decarboxylase activity probably reflects a reduced enzyme concentration. The enzyme half-life in vagotomized rats after histamine treatment was shorter than the half-life observed after inhibition of enzyme synthesis. Histamine administration may not only inhibit enzyme synthesis but may cause an accelerated rate of elimination of histidine decarboxylase. I.v. histamine infusion caused marked displacement of the pentagastrin dose-response curve, in a manner suggesting a reduced sensitivity to pentagastrin. After H2-receptor blockade but not after H1-receptor blockade, histamine was less effective in suppressing the enzyme activity. H2-receptor blockade augmented pentagastrin-induced enzyme activation. Histamine (via H2-receptors) may reduce sensitivity of the histamine-storing cells to gastrin, and H2-receptor blockade may induce the opposite effects. Histamine-storing cells in the rat stomach are possibly endowed with H2-receptors, and exogenous histamine may be capable of acting directly on histamine cells. This may reflect a physiological control mechanism whereby mobilized endogenous histamine modifies its own synthesis and release.