Acute effects of N‐terminal progastrin fragments on gastric acid secretion in man

We previously identified an N‐terminal fragment of progastrin in human antrum and plasma, where it circulates in high concentrations. In this study, we examined the effects of N‐terminal progastrin fragments on gastric acid secretion by infusion in healthy individuals. Increasing doses of progastrin fragment 1‐35 were infused intravenously during constant gastric acid stimulation by gastrin‐17. In addition, the effects of progastrin fragment 1‐35, fragment 6‐35, and fragment 1‐19 on gastrin‐17 stimulated acid secretion were tested. The gastrin‐17 stimulated acid secretion decreased 30% after administration of a high dose of progastrin fragment 1‐35 (P < 0.05). In extension, a 1‐h infusion of fragment 1‐35 also decreased gastric acid output. In contrast, fragment 6‐35 did not affect acid secretion, and a single infusion of gastrin‐17 alone did not reveal fading of gastric acid output during the time course of the experiments. The results show that N‐terminal fragments of progastrin may acutely affect gastrin‐stimulated gastric acid secretion in vivo. Structure‐function analysis suggests that the N‐terminal pentapeptide of progastrin is required for the effect.