Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin-deficient mice

Background & Aims: Studies in gastrin-deficient mice have demonstrated crit ical roles for gastrin peptides in the regulation of gastric acid secretion , but the relative contributions of amidated (G-17) and glycine-extended (G 17-Gly) gastrin remain unclear, We examined the effects of these 2 forms of gastrin on acid secretion in gastrin-deficient mice. Methods: Sixty gastri n-deficient mice received infusions of saline, or 1, 6, or 14 days of amida ted 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 wit h 1, 2, or 5 nmol.kg(-1).h(-1) of G-17 or G-17 and G17-Gly. Add secretion w as determined 4 hours after pyloric ligation, and gastric tissue was proces sed 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, b ut coinfusion with G-17 resulted in significantly higher levels of acid sec retion at all doses examined than infusion with G-17 alone. The potentiatin g effect of G17-Gly on G-17-induced acid secretion was associated with incr eased parietal cell activation but was independent of changes in parietal a nd 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 a cid secretion and prevent parietal cell degradation. These results suggest that G17-Gly plays an important role in parietal cell function.