Cholecystokinin does not affect the pancreatic contents of epidermal growth factor or its receptor

Cholecystokinin (CCK) is a hormone with well-known secretory and trophic ef fects on the pancreas. This also is true for epidermal growth factor (EGF), which acts in a paracrine and autocrine way. The aim was to study the infl uence of CCK on cell proliferation in rat pancreas with special reference t o the expression of EGF, the EGF receptor, and phosphorylated tyrosine. Twe nty-four male Sprague-Dawley rats received either one single injection, or injections twice daily for 3 days of 6 mug sulfated CCK-8 (CCK-8S) subcutan eously in the neck. The same number of rats received injections of 1% bovin e serum albumin (BSA) in the same way. The rats were killed I, 3, or 6 hour s after the last injection. One hour before killing, they received 50 mg/kg of bromodeoxyuridine (BrdU) intraperitoneally. Plasma was collected for an alysis of CCK, The pancreas was dissected, and in situ hybridization using a probe for EGF mRNA was performed for semiquantification of gene expressio n. Immunocytochemistry using antibodies against the EGF receptor and phosph otyrosine was performed to examine the expression of the proteins, and agai nst BrdU for measuring the cell proliferation. A single injection of CCK-8S led to hyperCCKemia at 1 and 3 hours afterward. After 6 hours, plasma CCK had returned to the same levels as in control rats. The cell proliferation was unaffected. The rats that received CCK-8S injections for 3 days still h ad hyperCCKemia 6 hours after the last injection. The cell proliferation wa s increased by CCK, as indicated by the BrdU labeling. However, neither bod y weight nor pancreatic weight was affected. In controls, EGF was expressed all over the gland, but its receptor and phosphotyrosine were expressed on ly in ductal cells and in the islet cells of endocrine pancreas. There was no difference in the pancreatic staining of EGF, its receptor, or phosphoty rosine at the different time points studied. There was no difference in the staining of EGF and its receptor between CCK-8S- and BSA-treated animals, but phosphotyrosine staining was detectable in acinar cells after 3 days of CCK-8S injections. Thus CCK-8S causes hyperCCKemia with ensuing enhanced c ell proliferation in rat pancreas. This effect on the cell proliferation se ems to be a direct effect of CCK and not mediated by changes in the tissue levels of EGF or its receptor.