Do cholecystokinin antagonists increase cytosolic calcium in pancreatic acinar cells and thereby promote pancreatitis?

In a number of studies using animal models, and in a human study, cholecystokinin (CCK) antagonists ameliorated pancreatitis. In a recent report of a study in a rat model of obstructive acute pancreatitis, however, it was suggested that a potent CCK1 antagonist, L364,718, had proved harmful. This effect was attributed to an increase in free cytosolic calcium levels in pancreatic acinar cells. Our understanding of obstructive pancreatitis now rests on feedback mechanisms that control CCK levels and are disrupted when obstruction is present. CCK antagonism might interrupt the process of pancreatitis by reducing the increase in CCK levels that promotes enzyme release. This article reviews the findings obtained with CCK antagonists in several experimental models of pancreatitis and assesses the recent findings with L364,718 in that light.