Receptor-mediated internalization and secretion of cholecystokinin into rat pancreatic duct fluid.

We measured cholecystokinin (CCK) in pancreatic duct secretions (PDS) after infusion of different amounts of CCK-8 (the C-terminal octapeptide of cholecystokinin) into rats. Injection of 23, 46, and 92 ng of CCK-8 increased immunoreactive cholecystokinin in PDS by 3-, 13-, and 28-fold above basal levels within 30 min. Continuous intravenous infusion of CCK-8 (50 ng/min) into rats for 30 min, followed by a 30-min rest period, and then a final infusion of peptide for another 30 min increased CCK in PDS only during the final period by 12-fold to 500 pg/30 min. Neither gastrin nor oxidized CCK-8 were detected in PDS after intravenous infusion of each peptide. Administration of proglumide (ip), a CCK receptor antagonist, during continuous CCK infusion significantly reduced immunoreactive CCK levels in PDS to 2% of the control group (P less than or equal to 0.01). CCK was also rapidly internalized into dispersed pancreatic acinar cells in a temperature-dependent fashion, and this process was inhibited by proglumide. The above data suggest that CCK in PDS reflects a peptide-specific process that is receptor mediated. We propose that circulating cholecystokinin binds to specific receptors on pancreatic acinar cells, is internalized, and is then secreted into pancreatic duct fluid.