The role of endogenous gastrin in the activation of gastric histidine decarboxylase in the rat. Effect of antrectomy and vagal denervation.

Abstract

The activity of gastruc histidine decarboxylase in normal rats was markedly reduced after prolonged fasting. The reduction was reversed by feeding and by injection of gastrin, insulin (vagal stimulation) or carbachol. Feeding, vagal stimulation or treatment with parasympathomimetics released endogenous gastrin. The role of endogenous gastrin (believed to be located in the antrum) and of the vagus nerve in activating gastric histidine decarboxylase was studied in antrectomized and in vagally denervated rats. Antrectomy reduced the activation of gastric histidine decarboxylase induced by feeding and abolished that induced by the injection of insulin or carbachol (but not that induced by pentagastrin). Antral exclusion, on the other hand, caused a marked enzyme activation. These results indicate the existence of an antral agent (presumably gastrin) which mediated in the process of enzyme activation. The effect of antrectomy on gastric acid secretion was studied in rats fitted with chronic gastric fistulas. Antrectomy depressed basal acid secretion, but did not abolish the effect of insulin hypogylcemia on acid secretion. Vagal denervation (truncal vagotomy or selective vastric vagotomy) in combination with pyloroplasty caused a marked activation of the gastric histidine decarboxylase in fasted rats. This activation was totally abolished by combined vagotomy and antrectomy. Consequently, enzyme activation observed after vagotomy is induced by some agent from the antrum, possibly gastrin. The activation of gastric histidine decarboxylase seen upon truncal vagotomy was abolished not only by antrectomy but also by perfusion of the stomach with dilute hydrochloric acid. It is therefore suggested, that low antral pH inhibits the release of gastrin and that the elevated antral pH caused by vagotomy stimulates its release. In chronic fistula rats, vagotomy caused a profound decreased of acid secretion and inhibited the secretory response to insulin and pentagastrin. The following concept is advanced: The activity of gastric histidine decarboxylase is under the influence of endogenous gastrin. The influence of the vagus nerve on histidine decarboxylase is exerted via the gastrin-containing cell in the antrum and not by direct action on the cell containing the enzyme. The influence of the vagus on the gastrin cell has two facets, possibly constituting the components in a feed-back mechanism: a) vagal stimulation of the gastrin cell releases gastrin; b) vagal stimulation of the parietal cell causes acid hypersecretion, whicc inhibits gastrin release. Activation of gastrin histidine decarboxylase is a consequence of gastrin-induced stimulation of the enzyme-containing cell. Important factors regulating the gastrin release are the vagal activity and the antral pH.