GASTRIN MEDIATES THE GASTRIC-MUCOSAL PROLIFERATIVE RESPONSE TO FEEDING

The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin -specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemica l characteristics of this antibody were characterized by competitive r adioimmunoassay, and the in vivo immunoneutralizing properties were va lidated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immun ohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pe ntagastrin-stimulated gastric acid secretion and had no effect on chol ecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secreti on and CCK-stimulated pancreatic secretion. Pretreatment with gastrin- specific MAb 8 h before refeeding significantly reduced by 61% the num ber of BrdU-labeled cells in the oxyntic mucosal proliferative zone co mpared with control MAb-treated rats. These results demonstrate the im portance of endogenous gastrin in the proliferative response of the ox yntic mucosa to feeding in the rat.