CERULEIN AND GASTRIN(2-17 DS) REGULATE DIFFERENTLY SYNTHESIS OF SECRETORY ENZYMES, MESSENGER-RNA LEVELS AND CELL-PROLIFERATION IN PANCREATIC ACINAR-CELLS (AR4-2J)

In order to characterize the biological functions coupled to cholecystokinin (CCK) A and B receptors, the effects of gastrin(2-17 ds) and caerulein were compared. An isolated cell model, the pancreatic acinar cell line AR4-2J, was used and the experiments were carried out in serum-free media. Caerulein was found to evoke no mitogenic effects either alone or in the presence of the CCK antagonists L364,718 and CR1409. Gastrin(2-17 ds) increased cell proliferation by 2-fold with an IC50 of 150 pM, corresponding to the occupancy of the CCK B receptors. CR1409, at concentrations that fully occupied CCK B receptors, inhibited the gastrin(2-17 ds) effects. Caerulein enhanced chymotrypsinogen biosynthesis by 100% and the corresponding MRNA level by 75%; amylase biosynthesis and mRNA level were enhanced by 40 % only. Half-maximal increases in chymotrypsin activity and mRNA level were recorded in response to caerulein at concentrations of 100 pM and 50 pM respectively. Gastrin(2-17 ds) at 100 nM enhanced chymotrypsinogen biosynthesis by 26% and its mRNA level by 35%; these responses were lower than those evoked by 0.1 nM caerulein, Furthermore, CR1409 completely inhibited caerulein- and gastrin(2-17 ds)-stimulated chymotrypsinogen synthesis, with similar IC50 (4 muM). These results suggest that both peptides induced the synthesis of the secretory enzyme after occupancy of CCK A receptors.