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 effects 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 influence of CCK on cell proliferation in rat pancreas with special reference to the expression of EGF, the EGF receptor, and phosphorylated tyrosine. Twenty-four male Sprague-Dawley rats received either one single injection, or injections twice daily for 3 days of 6 microg sulfated CCK-8 (CCK-8S) subcutaneously in the neck. The same number of rats received injections of 1% bovine serum albumin (BSA) in the same way. The rats were killed 1, 3, or 6 hours after the last injection. One hour before killing, they received 50 mg/kg of bromodeoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and in situ hybridization using a probe for EGF mRNA was performed for semiquantification of gene expression. Immunocytochemistry using antibodies against the EGF receptor and phosphotyrosine was performed to examine the expression of the proteins, and against 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 had hyperCCKemia 6 hours after the last injection. The cell proliferation was increased by CCK, as indicated by the BrdU labeling. However, neither body weight nor pancreatic weight was affected. In controls, EGF was expressed all over the gland, but its receptor and phosphotyrosine were expressed only in ductal cells and in the islet cells of endocrine pancreas. There was no difference in the pancreatic staining of EGF, its receptor, or phosphotyrosine 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 cell proliferation in rat pancreas. This effect on the cell proliferation seems to be a direct effect of CCK and not mediated by changes in the tissue levels of EGF or its receptor.
Ohlsson
B
B
Department of Surgery, University of Lund, Sweden.
Rehfeld
J F
JF
Sundler
F
F
D000818:Animals; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000494:pharmacology; D066246:ErbB Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects*; D019000:Phosphotyrosine / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D002766:Cholecystokinin; D066246:ErbB Receptors; D001973:Bromodeoxyuridine