Overexpression of glycine-extended gastrin inhibits parietal cell loss and atrophy in the mouse stomach.
Recently we have reported synergistic effects between glycine-extended gastrin (G-gly) and amidated gastrin-17 on acid secretion in short-term infusion studies. In the present study, we examined the long-term effect of G-gly on the atrophy-promoting effects of amidated gastrin in the mouse stomach with or without Helicobacter infection. Transgenic mice overexpressing amidated gastrin (INS-GAS mice), G-gly (MTI/G-gly mice), and both peptides (INS-GAS/G-gly mice) were used for assessment of acid secretion and ulcer susceptibility and histologic examination and scoring of preneoplastic lesions in response to the 3 and 6 months Helicobacter felis (H. felis) infection. We found that MTI/G-gly mice had normal gastric histology and acid secretion. Double transgenic (INS-GAS/G-gly) mice showed 2-fold increases in acid secretion compared with INS-GAS mice. Acute peptic ulcers after pyloric ligation were noted in 50% of the INS-GAS/G-gly mice but in none of the INS-GAS mice at 6 months of age. Whereas male INS-GAS mice had a >50% decrease in the numbers of parietal cell and enterochromaffin-like cell at 6 months of age, the male double transgenic mice had no such decrease. Overexpression of G-gly reduced the scores of preneoplasia in the stomach; however, it did not prevent the development of amidated gastrin-dependent gastric cancer in both H. felis-infected mice and uninfected mice. We conclude that G-gly synergizes with amidated gastrin to stimulate acid secretion and inhibits parietal cell loss in INS-GAS/G-gly mice. The overexpression of G-gly seems to increase the susceptibility to peptic ulcer disease and delay the development of Helicobacter-mediated gastric preneoplasia in this model.
Cui
Guanglin
G
Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts.
Koh
Theodore J
TJ
Chen
Duan
D
Zhao
Chun-Mei
CM
Takaishi
Shigeo
S
Dockray
Graham J
GJ
Varro
Andrea
A
Rogers
Arlin B
AB
Fox
James G
JG
Wang
Timothy C
TC
D000818:Animals; D004198:Disease Susceptibility; D005755:Gastrins / Q000737:chemistry / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry*; D051379:Mice; D008822:Mice, Transgenic; D010295:Parietal Cells, Gastric / Q000473:pathology*; D010437:Peptic Ulcer / Q000150:complications; D013270:Stomach / Q000473:pathology*
D005755:Gastrins; D005998:Glycine