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1. Pancreatic volume flow as well as bicarbonate and protein secretion from pancreatic fistulas have been measured in response to i.v. infusion of graded doses of bombesin and related peptides containing the COOH‐terminal fragment of the bombesin molecule in conscious dogs with intact antrum and in anaesthetized animals with antrectomy, or antrectomy and enterectomy. 2. Bombesin and related peptides given to conscious dogs produced a potent and dose‐dependent increase in pancreatic protein output reaching a maximum equal to that induced by the octapeptide of cholecystokinin (OP‐CCK) as well as a small rise in bicarbonate output attaining a peak amounting to about 10% of that evoked by secretin. The serum gastrin level rose progressively during the infusion of bombesin to reach a peak with the highest dose of peptide. 3. Bombesin infused i.v. in anaesthetized animals with resected antrum also evoked a marked increase in pancreatic protein secretion without significant changes in the serum gastrin level. Following the removal of the antrum and small intestine, bombesin failed to show any stimulation of the pancreatic secretion or any change in the serum gastrin level. It is concluded that the strong stimulatory action of bombesin and related peptides on pancreatic secretion cannot be entirely ascribed to the release of gastrin but might be attributed at least in part to the release of intestinal hormones, particularly CCK. 4. Atropine and the growth hormone‐release inhibiting hormone (GH‐RIH), which were shown to inhibit the release of CCK induced by duodenal perfusion of an amino acid mixture, also caused the inhibition of pancreatic protein secretion by bombesin but failed to affect the pancreatic response to OP‐CCK. The results indicate that bombesin releases, in addition to gastrin, CCK from the gut by a mechanism largely dependent upon cholingeric innervation.

1. Gastric and pancreatic secretion as well as serum gastrin an insulin levels have been measured after sham‐feeding, real feeding or exogenous hormonal stimulation in conscious dogs receiving (pyro) Glu‐His‐Gly, an appetite depressing peptide (AP). 2. Sham‐feeding produced a marked increase in gastric acid and pepsin outputs accompanied by an elevation of serum gastrin and insulin concentrations. AP infusion before and after sham‐feeding reduced the peak gastric secretion and suppressed gastrin and insulin responses to sham‐feeding. 3. Liver extract meal administered into the stomach resulted in an increase in gastric acid and serum gastrin and insulin levels. AP inhibited acid response to liver extract without affecting serum hormonal levels. Pentagastrin stimulation produced similar acid secretion to that obtained with liver extract and AP infusion also inhibited this secretion. 4. Secretin infusion or feeding a meat meal produced a similar rate of pancreatic bicarbonate secretion in dogs with chronic pancreatic fistula. AP infusion inhibited the bicarbonate response to feeding or secretin without affecting serum gastrin or insulin levels. 5. This study demonstrates that pyro‐Glo‐His‐Gly suppresses serum hormonal and gastric secretory response to cephalic stimulation and reduces gastrin and pancreatic secretory responses to ordinary feeding or exogenous hormonal stimuli.

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.

This study compares the gastrointestinal effects of somatostatin (SS) and its putative prohormone, prosomatostatin (Pro-SS), a 28-amino acid peptide isolated from the hypothalamus and the gut, in conscious dogs with chronic gastric and pancreatic fistulae. Pro-Ss suppressed the release of serum gastrin, insulin, and pancreatic polypeptide that occurs in response to feeding a meat meal in a manner similar to that seen with SS. However, in contrast to SS, which strongly reduced intestinal blood flow and oxygen consumption and stimulated intestinal motility, Pro-SS, at the doses tested, had no influence on mesenteric circulation, oxygen uptake, and intestinal motility. We conclude that Pro-SS mimics most of the gastrointestinal secretory actions of SS, but does not exhibit the intestinal circulatory, metabolic, and motor effects of SS.

1. Gastric acid responses to the test meals were measured in the Heidenhain pouch, gastric and pancreatic fistula dogs, using the intragastric titration method, and monitoring the rate at which a solution of 1‐0 N‐NaOH had to be added to maintain the pH of the gastric content constant at pre‐selected values ranging from 5‐0 to 1‐0. In this way the pH profile of the gastric acid and pepsin responses to a liver extract meal kept in the Heidenhain pouch or gastric fistula as well as to exogenous stimuli such as histamine, pentagastrin or Urecholine could be determined. 2. A liver extract meal adjusted to pH 5‐0 produced a potent and pressure‐related stimulation of acid secretion from the Heidenhain pouch without any change in secretion from the main stomach and pancreas or in the serum concentration of immuno‐assayable gastrin. 3. Graded decrease of the liver extract meal pH to below 5‐0 resulted in the pH‐dependent inhibition of gastric acid output, which at pH 1‐0 was only about 30% of the value attained at pH 5‐0. Acid secretion from the Heidenhain pouch induced by exogenous stimuli such as histamine, pentagastrin or Urecholine also showed gradual decrease when the pH of the pouch content was decreased in sequential order from 5‐0 to 1‐0. This pH‐dependent inhibition was accompanied by an increase in pepsin secretion. 4. The pH‐dependent inhibition of the Heidenhain pouch response to the liver extract meal was not altered by topical application of a local anaesthetic and atropine or by the intravenous infusion of large doses of atropine, secretin or metiamide, which were shown to cause a marked inhibition of the main stomach response to the liver meal. 5. The results indicate that there is a local and gastrin‐independent inhibition mechanism of gastric acid secretion activated by an acidified meal making contact with the oxyntic gland area.

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. Pancreatic bicarbonate and protein secretion as well as immuno‐reactive plasma secretin concentration in response to a meal, duodenal acidification and exogenous secretin or octapeptide of cholecystokinin (OP‐CCK) have been measured following administration of methionine‐enkephalin in chronic pancreatic fistula dogs. 2. Methionine‐enkephalin inhibited pancreatic responses to both exogenous hormones (secretin and OP‐CCK) and to endogenous hormones released from the gut by food or duodenal acidification. 3. Naloxone, a potent opiate receptor antagonist, partly prevents this methionine‐enkephalin‐induced inhibition of pancreatic secretion suggesting that this effect might be mediated by opiate receptors. 4. The inhibitory effect of methionine‐enkephalin on pancreatic response to endogenous stimulants was more pronounced than that to exogenous hormones and was accompanied by a significant reduction in plasma immuno‐reactive secretin concentration. 5. This study indicates that methionine‐enkephalin inhibits pancreatic secretion, at least in part, by suppressing the release of the intestinal hormones stimulating the exocrine pancreas.

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.