title: Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin-deficient mice.
abstract: OBJECTIVE
  Studies in gastrin-deficient mice have demonstrated critical roles for gastrin peptides in the regulation of gastric acid secretion, but the relative contributions of amidated (G-17) and glycine-extended (G17-Gly) gastrin remain unclear. We examined the effects of these 2 forms of gastrin on acid secretion in gastrin-deficient mice.
  
  
  METHODS
  Sixty gastrin-deficient mice received infusions of saline, or 1, 6, or 14 days of amidated gastrin 17 (G-17), G17-Gly, or both G-17 and G17-Gly at 10 nmol. kg(-1). h(-1). Twenty-four gastrin-deficient mice were then infused for 14 days with 1, 2, or 5 nmol. kg(-1). h(-1) of G-17 or G-17 and G17-Gly. Acid secretion was determined 4 hours after pyloric ligation, and gastric tissue was processed for histology, immunohistochemistry, and electron microscopy.
  
  
  RESULTS
  Infusion of G-17 increased acid secretion in a dose-dependent manner with a peak at 5 nmol. kg(-1). h(-1) and a subsequent decrease in acid secretion at higher doses. Infusion of G17-Gly alone had no effect on acid secretion, but coinfusion with G-17 resulted in significantly higher levels of acid secretion at all doses examined than infusion with G-17 alone. The potentiating effect of G17-Gly on G-17-induced acid secretion was associated with increased parietal cell activation but was independent of changes in parietal and enterochromaffin-like cell number, fundic proliferation rates, and H(+),K(+)-adenine triphosphatase expression. G17-Gly also prevented the formation of vacuolar canaliculi and lipofuscin bodies in the parietal cells induced by G-17.
  
  
  CONCLUSIONS
  G17-Gly appears to synergize with G-17 to up-regulate acid secretion and prevent parietal cell degradation. These results suggest that G17-Gly plays an important role in parietal cell function.
authors.affiliation: Department of Surgery and Laboratory Medicine, Trondheim University Hospital, Trondheim, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: C M
authors.initials: CM
authors.lastname: Zhao
authors.forename: G J
authors.initials: GJ
authors.lastname: Dockray
authors.forename: A
authors.initials: A
authors.lastname: Varro
authors.forename: A
authors.initials: A
authors.lastname: Van Hoek
authors.forename: N F
authors.initials: NF
authors.lastname: Sinclair
authors.forename: T C
authors.initials: TC
authors.lastname: Wang
authors.forename: T J
authors.initials: TJ
authors.lastname: Koh
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006965:Hyperplasia; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D013270:Stomach / Q000201:enzymology
chemical_list: D005755:Gastrins; C086854:glycine-extended gastrin 17; C013550:gastrin 17; D017506:H(+)-K(+)-Exchanging ATPase