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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.

Gastric inhibitory polypeptide (GIP), given to dogs in graded doses (range 0.25–2 µg/kg/hr) against a constant background stimulation with pentagastrin (4 µg/kg/hr), failed to affect the acid secretion at all doses used except the largest one (2 µg/kg/hr) which significantly reduced the acid secretion only from the vagally denervated portion of the stomach (Heidenhain pouch, HP) while raising plasma GIP two to three times above the levels reached with duodenal fat. GIP infused in a constant dose (1 µg/kg/hr) significantly reduced the HP responses to lower (0.5–2 µg/kg/hr) but not to higher (4–16 µg/kg/hr) doses of pentagastrin, the kinetics of this inhibition being of competitive type. GIP was ineffective against a constant near maximal stimulation with pentagastrin (4 µg/kg/hr), histamine (40 µg/kg/hr), or liver extract meal, whereas fat (10 g), given intraduodenally or intravenously, was a powerful inhibitor of acid responses to these stimulants both from the innervated and denervated stomach. Plasma GIP reached similar levels with exogenous GIP and duodenal fat but remained unchanged with intravenous infusion of fat.

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.

This study was designed to determine gastric alkaline secretion (GAS) and duodenal alkaline secretion (DAS) and their relation to the duodenal motility pattern in conscious dogs under basal conditions and after vagal stimulation by sham-feeding and insulin hypoglycaemia. GAS was measured in the gastric perfusate and DAS was determined in the perfusate of the upper duodenum (7 cm in length between occluding balloons). Resting GAS and DAS showed typical periodicity in phase with myoelectric and motor activity, reaching peaks during phases II and III, respectively, and nadir during phase I of the migrating motor cycle (MMC). Vagal excitation by sham-feeding or insulin hypoglycaemia resulted in an immediate rise in GAS and DAS, accompanied by a suppression of MMC. Atropine (25 ug/kg) reduced basal GAS and DAS by about 50% and abolished GAS but not DAS in response to vagal stimulation, being accompanied by complete suppression of MMC for several hours. Following injection of indomethacin (2.5 mg/kg) to suppress the generation of endogenous prostaglandins, a prolonged reduction in basal GAS and DAS and an increase in the myoelectric activity and the disruption of the MMC occurred. Neither GAS nor DAS responses to vagal stimulation were affected by indomethacin. We conclude that resting GAS and DAS fluctuate cyclically in phase with gastroduodenal motor activity, and that vagal excitation results in a potent stimulation of alkaline secretion and myoelectric activity which are, in part, cholinergic and do not depend upon the generation of endogenous prostaglandins.

Exocrine pancreatic response to food is believed to result from the interaction of neural and hormonal factors, but their contribution in the net postprandial secretion is unknown. Recent description of a highly specific and potent Cholecystokinin (CCK)-receptor antagonist permitted the evaluation of the physiologic role of CCK in postprandial pancreatic secretion. In dogs with chronic pancreatic fistula, CCK antagonism caused little alteration in sham feeding- or urecholine-induced pancreatic protein secretion, but reduced by ~60% the pancreatic protein response to a gastrointestinal meal and virtually abolished the pancreatic responses to duodenal perfusion with amino acids or oleate and to exogenous CCK, but not to secretin or neurotensin. The pancreatic protein responses, particularly to lower doses of gastrin, were also reduced by CCK-receptor antagonist, but no changes in the responses to secretin or neurotensin were detected. Cholecystokinin antagonism also significantly reduced the pancreatic polypeptide responses to CCK, gastrin, and the gastrointestinal meal, possibly due to removal of the CCK-mediated release of pancreatic polypeptide. We conclude that CCK plays a crucial role in the mediation of the gastrointestinal phase, but not the cephalic phase, of pancreatic secretion.

This study was undertaken to determine gastric acid response to histamine applied topically to the mucosal surface and to examine the local effect of ranitidine, a histamine H2-receptor antagonist, on the gastric acid response to histamine. Histamine applied to the Heidenhain pouch (HP) mucosa resulted in a slight and dose-dependent stimulation of acid secretion without affecting acid secretion from the main stomach. Ranitidine given into the HP caused dose-dependent inhibition of the HP response to topical or intravenous histamine without affecting the acid response of the main stomach and without any significant change in the serum ranitidine level. Ranitidine applied to the main stomach with the pylorus occluded inhibited histamineinduced acid secretion also without any increase in the serum ranitidine level. This inhibition was about 30% of that obtained with the same dose of ranitidine given into the stomach with the pylorus left open during the experiment. This study provides evidence that topical hsitamine is a weak stimulant of gastric secretion and that topical ranitidine is capable of local inhibition of the acid response to both topical or intravenous histamine.