Synergistic Effects of Bombesin and Cholecystokinin on Cholesterol Esterase Biosynthesis and Secretion by Ar42J Cells

Abstract

This study used the rat pancreatoma AR42J cells as model to study hormonal regulation of cholesterol esterase biosynthesis. Our previous studies (Y. Huang and D. Y. Hui, 1991, J. Biol. Chem. 266, 6720-6725) have demonstrated that the AR42J cells responded to cholecystokinin (CCK) and secretin challenge by increasing cholesterol esterase biosynthesis. The current investigation showed that another gastric peptide hormone, bombesin, was also effective in stimulation of cholesterol esterase biosynthesis. Cholesterol esterase biosynthesis in AR42J cells increased 2- to 3-fold in the presence of 5 to 10 nm bombesin or 4 nm CCK. More significantly, when both bombesin and CCK were added to the incubation medium at these concentrations simultaneously, a 15-fold induction of cholesterol esterase biosynthesis was observed. Slot-blot analysis of RNA isolated from control and hormone-stimulated cells revealed no change in the level of cholesterol esterase mRNA, suggesting the post-transcriptional activation of cholesterol esterase biosynthesis. The synergism between bombesin and CCK was not restricted to cholesterol esterase biosynthesis as the simultaneous addition of the two hormones also dramatically increased amylase secretion by AR42J. The results of these studies indicated that gastric peptide hormones may act in concert to stimulate maximally digestive enzyme biosynthesis. The synergistic effects of bombesin and CCK also suggest that distinctive signal transduction pathways may be responsible for the bombesin and CCK induction of pancreatic protein secretion.