gastrins and Pancreatic-Fistula

Topics: Animals; Dogs; Duodenum; Gastric Fistula; Gastric Juice; Gastrins; Hydrochloric Acid; Hydrogen-Ion Concentration; Insulin; Pancreas; Pancreatic Fistula; Peptides; Secretin; Sympathectomy

This study was designed to determine the role of cholecystokinin (CCK) in the inhibition of gastric HCl secretion by duodenal peptone, fat and acid in dogs with chronic gastric and pancreatic fistulas. Intraduodenal instillation of 5% peptone stimulated both gastric HCl secretion and pancreatic protein secretion and caused significant increments in plasma gastrin and CCK levels. L-364,718, a selective antagonist of CCK-A receptors, caused further increase in gastric HCl and plasma gastrin responses to duodenal peptone but reduced the pancreatic protein outputs in these tests by about 75%. L-365,260, an antagonist of type B receptors, reduced gastric acid by about 25% but failed to influence pancreatic response to duodenal peptone. Addition of 10% oleate or acidification of peptone to pH 3.0 profoundly inhibited acid secretion while significantly increasing the pancreatic protein secretion and plasma CCK levels. Administration of L-364,718 reversed the fall in gastric HCl secretion and significantly attenuated pancreatic protein secretion in tests with both peptone plus oleate and peptone plus acid. Exogenous CCK infused i.v. in a dose (25 pmol/kg per h) that raised plasma CCK to the level similar to that achieved by peptone meal plus fat resulted in similar inhibition of gastric acid response to that attained with fat and this effect was completely abolished by the pretreatment with L-364,718. We conclude that CCK released by intestinal peptone meal, containing fat or acid, exerts a tonic inhibitory influence on gastric acid secretion and gastrin release through the CCK-A receptors.

Topics: Animals; Benzodiazepinones; Bethanechol Compounds; Cholecystokinin; Devazepide; Dogs; Gastric Acid; Gastric Fistula; Gastrins; Histamine; Hydrogen-Ion Concentration; Oleic Acid; Oleic Acids; Pancreatic Fistula; Peptones; Phenylurea Compounds; Receptors, Cholecystokinin; Sincalide

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 approximately 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.

Topics: Animals; Cholecystokinin; Dogs; Food; Gastric Fistula; Gastrins; Glutamine; Pancreas; Pancreatic Fistula; Pancreatic Polypeptide; Proglumide; Receptors, Cholecystokinin

To determine the role of endogenous pancreatic polypeptide (PP) as a physiological inhibitor of pancreatic secretion, normal rabbit serum (control) or rabbit PP-antiserum was administered intravenously to dogs with chronic esophageal, gastric, and pancreatic fistulas. In all dogs tested, sham-feeding and ordinary feed with a meat meal resulted in a marked rise in the plasma level of immunoreactive PP that coincided with an increase in the exocrine pancreatic secretion of HCO3- and protein. After intravenous administration of PP antiserum, endogenous plasma PP was almost completely bound by infused antibodies to PP, whereas no such binding was detected after infusion of normal rabbit serum. In contrast, plasma gastrin remained unchanged both under basal and stimulated conditions. Immunoneutralization of PP, released endogenously, failed significantly to affect gastric acid and pancreatic protein responses to sham-feeding and the pancreatic HCO3- and protein responses to feeding a meat meal in chronic pancreatic fistula dogs. However, the PP antiserum abolished, in part, the inhibitory effect of exogenous PP on pancreatic secretion stimulated by exogenous hormones. We conclude that endogenous PP is not a physiological inhibitor of exocrine pancreatic secretion, as has been suggested previously.

Topics: Animals; Antibodies; Bicarbonates; Dogs; Eating; Esophageal Fistula; Gastric Acid; Gastric Fistula; Gastrins; Islets of Langerhans; Pancreatic Fistula; Pancreatic Polypeptide; Proteins; Rabbits; Secretin; Sincalide

The responses of exocrine pancreas, plasma secretin, and gastrin to a test meal were studied in six dogs prepared with gastric and duodenal fistulas. The experiment was doubly repeated in each dog. Pancreatic juice was diverted to the exterior by direct cannulation into the major pancreatic duct. Volume, bicarbonate, and protein secretion of pancreatic juice were rapidly increased and then gradually reduced after the ingestion of the meal. Plasma secretin concentration reached a peak at 25 min after the ingestion of the meal and remained higher than the basal level for about 3 h. Plasma gastrin concentration rapidly reached a higher plateau which lasted for 40 min after the load of the test meal. A close correlation was observed between bicarbonate secretion and the increment in plasma secretin concentration and between protein secretion and the increment in plasma gastrin concentration. When pancreatic juice is diverted to the exterior, endogenously released secretin and gastrin appear to play an important role in postprandial pancreatic secretion.

Topics: Animals; Bicarbonates; Dogs; Eating; Gastrins; Pancreatic Fistula; Pancreatic Juice; Secretin

It is well established that massive small-bowel resection (MSBR) invariably causes hypersecretion of acid in animals with denervated gastric pouches. The effect of MSBR on the secretory responses of both the totally innervated stomach and pancreas have been less well studied. Eighteen adult mongrel dogs were prepared with chronic gastric and pancreatic fistulae. In eight, massive small-bowel resection was performed in addition. Bowel resection did not alter the responses to graded doses of pentagastrin. However, in response to the intragastric titration of a liver extract meal, it had the following effects: (1) profound gastric acid hyposecretion; (2) reduction in pancreatic bicarbonate and protein secretion; and (3) increase in basal and meal-stimulated serum glucagon levels. Hypergastrinemia did not occur after resection. The hyposecretory responses may represent either increased inhibition or decreased secretory stimulation.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Fatty Acid-Binding Proteins; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Intestine, Small; Liver Extracts; Pancreas; Pancreatic Fistula; Pentagastrin; Peptides; Stomach

Topics: Animals; Dogs; Gastrins; Pancreas; Pancreatic Fistula; Pancreatic Juice; Secretin

We compared the inhibition of food-stimulated gastric acid secretion and changes in serum concentrations of immunoreactive gastric inhibitory polypeptide and gastrin caused by: (a) duodenal perfusion of oleic acid, and (b) intravenous infusion of pure, natural, porcine gastric inhibitory, polypeptide in dogs with gastric fistula and pancreatic fistula. A rate of duodenal perfusion of oleic acid (12 ml/hr) which gave near maximal pancreatic protein response was chosen. This dose of oleic acid caused complete suppression of acid response to a meal of liver extract (300 ml of a 15% solution) while elevating serum immunoreactive gastric inhibitory polypeptide modestly. By contrast, intravenous administration of gastric inhibitory polypeptide that raised serum immunoreactive gastric inhibitory polypeptide several fold caused only 40% inhibition of acid response to the same meal. Other effects of duodenal perfusion of oleic acid were exaggeration of pancreatic protein secretion and significant inhibition of gastrin release in response to the meal. Exogenous administration of gastric inhibitory polypeptide, on the other hand, was without significant effect on these responses. These results suggest that, in the innervated dog stomach, the enterogastrone action of fat is not primarily mediated by gastric inhibitory polypeptide.

Topics: Animals; Cholecystokinin; Dogs; Eating; Gastric Fistula; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Oleic Acids; Pancreatic Fistula; Pancreatic Juice; Pentagastrin; Secretin

Topics: Animals; Dietary Fats; Dogs; Duodenum; Eating; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Lipid Metabolism; Oils; Oleic Acids; Pancreatic Fistula; Pancreatic Juice; Time Factors

Topics: Animals; Atropine; Bicarbonates; Chronic Disease; Dogs; Dose-Response Relationship, Drug; Ethanol; Gastric Fistula; Gastrins; Lidocaine; Pancreas; Pancreatic Fistula; Pancreatic Juice; Proteins; Secretin

Topics: Animals; Cholecystokinin; Dogs; Elasticity; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Insulin; Pancreatic Fistula; Pancreatic Juice; Pepsin A; Secretin; Stomach; Vagus Nerve; Water

Topics: Animals; Bicarbonates; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Iodine Isotopes; Pancreas; Pancreatic Fistula; Pancreatic Juice; Pepsin A; Proteins; Swine

Topics: Animals; Biliary Fistula; Cats; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Hydrochloric Acid; Pancreatic Fistula; Peptides

Topics: Animals; Cholecystokinin; Digestion; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Histamine; Pancreatic Fistula; Pancreatic Juice; Pharmacology; Pylorus; Research; Secretin; Stomach

Topics: Animals; Dogs; Gastric Juice; Gastrins; Pancreas Transplantation; Pancreatic Fistula; Pancreatic Juice; Pylorus; Secretory Rate

Topics: Animals; Cholecystokinin; Dogs; Gastric Fistula; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Injections, Intravenous; Injections, Subcutaneous; Intestinal Mucosa; Pancreas; Pancreatic Fistula; Secretin; Tissue Extracts