MODULATION OF PANCREATIC EXOCRINE FUNCTION IN RODENTS BY TREATMENT WITH PANCREATIC-POLYPEPTIDE

The in vivo and in vitro treatment effects of pancreatic polypeptide (PP) were characterized by studying agonist-stimulated enzyme secretion in pancreatic acini prepared from 8-week-old mice treated for 2 days with PP (200 mug kg-1 day-1) and in pancreatic lobules from untreated male rats. In the mouse studies, enzyme secretion was evaluated on the basis of percentage total amylase released, amylase released per unit of DNA, and amylase released per unit of protein. When expressed as percentage total amylase released, the acini from mice treated with PP were significantly less responsive to pancreatic secretogogues than were acini from control animals. Chronic treatment with bovine PP lowered the maximal response to carbachol (12.3 +/-0.3 vs. 9.0 +/- 0.3% total amylase release in control and PP treated, respectively), decreased the magnitude of the difference between basal and maximal amylase release (10.6 +/- 0.4 vs. 6.2 +/- 0.5% total amylase release in control and PP treated, respectively), and affected these changes without modifying the dose of carbachol producing half-maximal amylase release. Similarly, the percentage of total amylase released in response to all doses of cholecystokinin octapeptide (1-100 pM) was reduced by chronic treatment with PP. However, when amylase release was expressed relative to protein or DNA, no differences in enzyme release were detected between treatments with either secretagogue. Chronic treatment with PP increased the total amount of amylase in the acini (per unit DNA or protein), but the increased amylase appeared to be unavailable for release since the actual amount (per microgram DNA or milligram protein) released in response to agonists did not differ between treatments. In contrast to the effects of chronic treatment, acute treatment of isolated acini or lobules with PP had no effect on basal or on amylase release stimulated by secretagogues or agents such as scorpion toxin that act through intrapancreatic neural elements. The present findings argue against a direct effect of PP on the pancreas and support the suggestion that PP predominately affects pancreatic function through modulation of central vagal cholinergic tone.