Secretory capacity of pancreatic protein during luminal feedback regulation in conscious rats

Pancreatic exocrine secretion in conscious rats is regulated by bile and pancreatic juice in the proximal intestine (luminal feedback regulation), and bile-pancreatic juice diversion from the intestine results in cholecystokinin (CCK) release and pancreatic hypersecretion. Pancreatic protein secretion increases to a maximum 60-90 min after bile-pancreatic juice diversion, and then decreases slightly to a steady level of two times the basal level. Change in plasma CCK concentration parallels protein secretion. In this study, the mechanism of the decreases of protein secretion and CCK concentration was examined by stimulation with various species of peptides having different stimulatory mechanisms. Cannulae for draining bile and pancreatic juice separately and a duodenal cannula and extrajugular vein cannula were inserted into male Wistar rats. Four days later, basal levels in a 90-min period were determined, bile and pancreatic juice were diverted for 90 min, and then either secretin (1.2 nmol/kg/h), CCK-8 (25 and 100 pmol/kg/h), neuromedin C (350 pmol/kg/h and 3.5 nmol/kg/h), or CCK-JMV-180 (200 nmol/kg/h) was infused intravenously for 60 min. Infusion of secretin significantly increased protein secretion and prevented its decrease after its maximum induced by bile-pancreatic juice diversion. The plasma CCK concentrations were not increased further by neuromedin C. In conclusion, pancreatic exocrine secretion and CCK release in conscious rats are maximally stimulated by luminal feedback regulation that the decrease after maximal protein output may be due to limitation of secretory capacity and/or desensitization of acinar cells.