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

Abstract

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. Acinoductal transdifferentiation was induced in vitro by culturing of acinar cells, and ductular metaplasia was obtained in vivo by ligation of the pancreatic ducts. Mitogenic effects of gastrin I on ductal complexes in vivo and of tetragastrin, 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 reverse-transcription polymerase chain reaction were applied for detection of the CCK-B receptor. Gastrin analogues induced a mitogenic stimulus in the duct-like cells in vitro and in ductal complexes in duct-ligated rat pancreas. Immunocytochemistry showed expression of CCK-B receptors in these 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. Duct-like pancreatic epithelial cells in vitro and ductal complexes in vivo express gastrin/CCK-B receptors and proliferate in response to gastrin.