Expression of cholecystokinin in the pancreas during development

We have reported that cholecystokinin-like immunoreactivity (CCK-LI) and its transcripts are expressed in rat pancreatic islets (Endocrinology 1998;139:389-96). The purpose of this study was to elucidate the ontogeny of CCK during pancreatic development in the rat. Fetal rats from day 13 (E13) to 20 (E20) and postnatal (P) rats from day 1 to adulthood were used in this study. Immunohistochemical studies of rat pancreas were carried out with rabbit antisera against CCK-8 and gastrin-17. The absorption studies were performed by using CCK-8 antiserum incubated with excess CCK-8 or gastrin-17. In situ hybridization was performed to demonstrate the CCK and gastrin transcripts in the pancreas. CCK and gastrin were first detected at E15, and they were distributed in the periphery of the islets in the fetal and neonatal pancreas. The mirror sections for CCK revealed positive cells with characteristics identical to those that stained positive for gastrin. The CCK-LI in early development was completely abolished by preabsorption with excess gastrin but not with CCK-8. These findings indicated that the CCK-LI in the fetal and neonatal pancreas was crossreacting gastrin rather than CCK-8. From weaning (P21) through adulthood, on the other hand, CCK-LI was expressed diffusely in pancreatic islets, but there were no gastrin-positive cells after weaning. In situ hybridization showed that CCK messenger RNA (mRNA) was present in rat pancreatic islets in adults but not in early development. Although CCK-positive cells were not detected in fetal and neonatal pancreatic islets, CCK was expressed in islets during and after weaning through adulthood, indicating that CCK in pancreatic islets might be developmentally regulated.