title: Acute effects of N-terminal progastrin fragments on gastric acid secretion in man.
abstract: 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.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet University of Copenhagen, Copenhagen, Denmark JPG@dadlnet.dk.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
authors.affiliation: Department of Gastrointestinal Surgery, Rigshospitalet University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten P
authors.initials: CP
authors.lastname: Hansen
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
mesh_terms: D000328:Adult; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D005755:Gastrins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D005755:Gastrins; D010446:Peptide Fragments; D011498:Protein Precursors; C118842:progastrin (1-35); C013550:gastrin 17
keywords: Acid secretion; N‐terminal; inhibition; progastrin; regulation