Abstract
The gut hormone cholecystokinin (CCK) octapeptide stimulates the release of amylase from exocrine pancreas, a process believed to be the result of the breakdown of phosphatidylinositol lipids. To examine further the relationship between phosphoinositide (PI) breakdown and amylase release, we have investigated the effect of N-terminally protected CCK C-terminal fragments in these systems using guinea-pig pancreatic lobules. There was a good correlation between the ability of these fragments to elicit amylase release and their potency in enhancing PI breakdown. In general, the EC50 for amylase release is 10-fold lower than the EC50 for PI breakdown. In addition, a good correlation existed between amylase release and the affinity of CCK fragments for [125I]Bolton Hunter-CCK octapeptide binding sites in pancreatic membranes. We also discovered that N-carbobenzyloxy-CCK tetrapeptide was relatively inefficient in causing PI breakdown, but it caused a near maximal stimulation in amylase release. These findings might reflect an amplification mechanism between PI breakdown and amylase release or that N-carbobenzyloxy-CCK tetrapeptide-induced amylase release is independent of PI breakdown.