Acute effects of N-terminal progastrin fragments on gastric acid secretion in man
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Acute effects of N-terminal progastrin fragments on gastric acid secretion in man. / Goetze, Jens P; Hansen, Carsten P; Rehfeld, Jens F.
I: Physiological Reports, Bind 5, Nr. 5, e13164, 2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Acute effects of N-terminal progastrin fragments on gastric acid secretion in man
AU - Goetze, Jens P
AU - Hansen, Carsten P
AU - Rehfeld, Jens F
N1 - © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Adult
KW - Female
KW - Gastric Acid/secretion
KW - Gastric Mucosa/drug effects
KW - Gastrins/pharmacology
KW - Humans
KW - Male
KW - Peptide Fragments/pharmacology
KW - Protein Precursors/pharmacology
KW - Young Adult
U2 - 10.14814/phy2.13164
DO - 10.14814/phy2.13164
M3 - Journal article
C2 - 28275110
VL - 5
JO - Physiological Reports
JF - Physiological Reports
SN - 2051-817X
IS - 5
M1 - e13164
ER -
ID: 196133419