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

Abstract

Background & Aims: 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.GASTROENTEROLOGY 2000;119:756-765