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.
Izzo
R S
RS
Department of Medicine, Nassau County Medical Center, East Meadow, New York 11554.
Praissman
M
M
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000378:metabolism; D008297:Male; D010183:Pancreatic Ducts / Q000378:metabolism*; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology
D005755:Gastrins; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D011377:Proglumide; D012844:Sincalide