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1. Gastric acid and pancreatic bicarbonate and protein secretion as well as immunoreactive serum gastrin and pancreatic polypeptide concentrations in response to a meal and secretin have been measured before and after infusion of bovine pancreatic polypeptide or its C‐terminal hexapeptide. 2. Liver extract meal kept in the stomach at pH 5.5 (by intragastric titration) produced a marked increase in gastric acid and pancreatic protein secretion accompanied by a rise in serum gastrin and pancreatic polypeptide levels. Exogenous bovine pancreatic polypeptide caused little change in gastric secretion and serum gastrin but resulted in a profound suppression of pancreatic secretion. 3. Ordinary feeding a liver meal produced a marked increase in pancreatic bicarbonate and protein secretion that was dose‐dependently inhibited by bovine pancreatic polypeptide or its C‐terminal hexapeptide, the degree of inhibition being closely correlated with the increments in plasma pancreatic polypeptide. 4. Bovine pancreatic polypeptide and its C‐terminal hexapeptide also inhibited secretin and caerulein‐induced pancreatic secretion in a dose‐dependent manner. 5. This study shows that bovine pancreatic polypeptide inhibits pancreatic secretion at least in part by acting directly on the exocrine pancreas and that its biological activity resides in its C‐terminal hexapeptide fragment.

1. The serum gastrin level, gastric mucosal blood flow and acid secretion from the canine Heidenhain pouch have been measured in response to the introduction of bovine serum albumin, pepsin‐digested albumin, an amino acid mixture, liver extract and mannitol used as control. 2. Distention of the Heidenhain pouch with mannitol or albumnin at pH 5‐0 produced a similar pressure‐related increase of acid secretion reaching a peak of only 10 percent of the maximal response to histamine. Pepsin‐digested albumin was capable of producing larger acid outputs than undigested albumin.The highest acid output, attaining about 80 percent of the maximal response to histamine, was obtained with liver extract both before and after exhaustive dialysis to remove all the amino acids and short peptide fragments. An amino acid mixture containing all essential amino acids was also found to stimulate acid secretion but a lesser degree than liver extract. 3. This concluded that it is not the intact protein but the products of its digestion, the polypeptides and free amino acids, which are potent chemical stimulants of acid secretion from the oxyntic gland area. Since the serum gastrin level was not changed during acid secretion induced by peptic digests bathing the oxyntic gland area, the mechanism of chemical stimulation appears to be gastrin‐independent. 4. The response to chemical stimulation by peptic digests can be greatly potentiated by combining this with distention of the oxyntic gland area. Topical application of xylocaine or atropine causes a marked decrease of Heidenhain pouch response to peptic digests, suggesting a possible neural reflex component in the mechanism of chemical stimulation of the oxyntic gland area. 5. When the pH of the liver extract in the Heidenhain pouch was gradually decreased in sequential order from 5–0 to 1–0, this resulted in a pH‐related decrease in acid secretion and in the mucosal blood flow falling to the basal level at pH 1–0. Exogenous secretion given in graded doses from 0–5 to 8–0 u./kg. hr caused a small but dose‐related inhibition of acid response to liver extract accompanied by a decrease of mucosal blood flow but without any significant change in the serum gastrin level. 6. The results indicate that the chemical stimulation of the oxyntic gland area by peptic digests is capable of inducing acid secretion by a local, gastrin‐independent, partially neural reflex mechanism; sensitive to pH, pressure and secretin.

1. This study was designed to determine the involvement of cholecystokinin (CCK) in the gastric secretory responses to exogenous and endogenous secretagogues in conscious dogs with chronic gastric fistulae (GF), pancreatic fistulae (PF) and Heidenhain pouches (HP). 2. A meal of meat or intragastric application of peptone (300 mosM) increased secretion of HCl from the HP and pancreatic secretion of protein and plasma levels of gastrin, CCK and somatostatin. 3. The CCK receptor antagonist L‐364,718 caused a further increase in the postprandial HCl secretion from the HP and in the plasma levels of gastrin and CCK but pancreatic output of protein and plasma concentration of somatostatin were significantly reduced. 4. Addition to intragastric peptone of 10% oleate or its acidification to pH 3.0 profoundly inhibited the HP secretion and gastrin release but significantly increased pancreatic secretion of protein and plasma levels of CCK and somatostatin. Administration of L‐364,718 reversed the fall in the HP secretion and plasma gastrin while significantly attenuating pancreatic protein secretion and plasma somatostatin levels. 5. Intragastric administration of hyperosmolar (1200 mosM) peptone also inhibited HCl secretion from the HP but this was not affected by L‐364,718. 6. Exogenous CCK and bombesin (but not gastrin) caused a small increase in HCl secretion from the HP and marked stimulation of pancreatic protein secretion accompanied by a significant rise in plasma levels of gastrin, CCK and somatostatin. Administration of L‐364,718 resulted in a further increase in the HCl response of HP to bombesin and in plasma levels of gastrin and CCK but caused a reduction in plasma levels of somatostatin. 7. We conclude that CCK released by a meal of meat, intragastric peptone, oleate or acidified peptone and intravenous bombesin exerts tonic inhibitory influences on gastric acid secretion and that this effect is mediated, at least in part, by somatostatin.