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The response of pancreatic polypeptide (PP) to testmeal (5 ml/kg) and intraduodenal acid (4 mEq HCl/5min) and its reaction to somatostatin (3.5 microgram/kg/h following bolus injection of 3.5 microgram/kg) was studied in dogs with chronic duodenal and gastric fistulae. In addition the influence of atropin (0.5 mg/kg/h) on acid-induced PP response was examined. PP was measured by radioimmunoassay pancreatic secretion by determinating volume, bicarbonate, protein, and enzyme in duodenal contents and pancreatic juice. Plasma PP increased significantly following intraduodenal application of testmeal and hydrochloric acid. Its release was completely suppressed by SST. Furthermore, PP response to intraduodenal acid was blocked by atropin. Exocrine pancreatic secretion of bicarbonate and protein was inhibited by somatostatin as well as atropin. Since PP was released following administration of testmeal and acid, both potent stimulators of pancreatotropic duodenal hormones, it may play an important role in the control of the entero-pancreatic axis. The effect of atropin indicates a cholinergic nervous component of PP release.