Different effects of hyperstimulation by similar classes of secretagogues on the exocrine pancreas

Cholecystokinin and its analogues such as cerulein, muscarinic cholinergic agonists, and gastrin-releasing peptide (bombesin) bind to distinct receptors on the surface of pancreatic acinar cells and stimulate digestive protein secretion by a calcium-dependent mechanism. The mechanisms of the calcium-dependent secretagogue classes has been assumed to be similar. In this study we have noted that dispersed pancreatic acini secrete comparable maximal rates of amylase in response to cerulein and bombesin; however, the maximal level of phosphatidylinositol 4,5-bisphosphate hydrolysis was less with bombesin than with cerulein. The high agonist dose-inhibited secretion in vitro observed with cerulein was absent with bombesin. In vivo administration of supramaximal secretory stimulating doses of both cerulein and bombesin caused pancreatic edema; however, the increase in serum concentrations of amylase and lipase induced by cerulein treatment was not detected with bombesin. These data indicate that cerulein and bombesin display distinctly different effects on the exocrine pancreas both in vivo and in vitro. That pancreatic edema and elevated serum enzyme levels may be the result of different cellular mechanisms in experimental pancreatitis is strongly suggested.