Mitogenic effect of gastrin and expression of gastrin receptors in duct-like cells of rat pancreas

Background & Aims: Ductular metaplastic cells are observed during pancreas injury. Growth control by gastrin and expression of gastrin/cholecystokinin (CCK) B receptors were evaluated in these cells. Methods: Acinoductal tran sdifferentiation was induced in vitro by culturing of acinar cells, and duc tular metaplasia was obtained in vivo by ligation of the pancreatic ducts. Mitogenic effects of gastrin I on ductal complexes in vivo and of tetragast rin, pentagastrin, and gastrin I and II, with or without the CCK-B receptor antagonist L-365,260, on duct-like cells in vitro were analyzed by 5-bromo -2 ' -deoxyuridine labeling. Immunocytochemistry, Western blotting, and rev erse-transcription polymerase chain reaction were applied for detection of the CCK-B receptor. Results: Gastrin analogues induced a mitogenic stimulus in the duct-like cells in vitro and in ductal complexes in duct-ligated ra t pancreas. Immunocytochemistry showed expression of CCK-B receptors in the se models and in fetal but not normal adult exocrine pancreas. Additionally , up-regulation of CCK-B receptors during ductular metaplasia was shown by Western blotting and reverse-transcription polymerase chain reaction. Concl usions: Duct-like pancreatic epithelia[ cells in vitro and ductal complexes in vivo express gastrin/CCK-B receptors and proliferate in response to gas trin.