Biological activity of carboxy-terminal gastrin analogs

Amidated forms of gastrin are derived by post-translational processing of a large precursor peptide and stimulate gastric acid secretion via the gastr in/CCKB receptor. Non-amidated biosynthetic intermediates may exert biologi cal effects through other mechanisms, but their effect on gastric acid secr etion is unclear. Amidated gastrins stimulate acid secretion mainly by rele asing histamine from mucosal enterochromaffin-like cells. This study examin es the effects on histamine release from the vascularly perfused rat stomac h of amidated gastrin-17, COOH-terminal glycine-extended gastrin-17, gastri n-17 extended at the COOH-terminal including the remaining progastrin seque nce, and carboxy-terminal progastrin fragments (SAEDEN and GRRSAEDEN). Carb oxy-terminal extended gastrins induced histamine release which was inhibite d by the gastrin/CCKB antagonist L-740,093, but had to be given in concentr ations 100-fold higher than amidated gastrin-17 to produce comparable effec ts. These progastrin-derived peptides are found in high concentrations in s ome patients with the Zollinger-Ellison syndrome and may contribute to acid hypersecretion and other gastrin/CCKB receptor mediated responses. (C) 199 9 Elsevier Science B.V. All rights reserved.