sincalide and Pancreatic-Fistula

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

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

In dogs with pancreatic fistulas, meat feeding and intestinal perfusion with a sodium oleate or amino acid mixture increased pancreatic protein secretion to approximately 110, 100, and 50%, respectively, of the response to cholecystokinin (CCK) at a dose of 85 pmol X kg-1 X h-1. Plasma CCK response increased in these studies to approximately 100, 180, and 40%, respectively, of the value obtained with exogenous CCK, suggesting that, in addition to CCK, other neurohormonal factors contribute to pancreatic enzyme secretion in response to endogenous stimulants. Feeding and duodenal oleate or amino acids also stimulate the release of pancreatic polypeptide (PP), which may be involved in the control of pancreatic secretion in response to endogenous stimulants, including CCK. Perfusion of the intact intestine with graded amounts of oleate (0.5-16 mmol/h) produced dose-dependent increments in plasma CCK and pancreatic protein similar to those obtained with intravenous infusion of graded doses of CCK (0.85-255 pmol X kg-1 X h-1). Oleate perfusion of isolated Thiry loops (30 cm long) made of duodenojejunal (D-J) and ileal (I) segments also stimulated protein secretion but elevated plasma CCK only after perfusion of the D-J but not of the I loop. We conclude that 1) the endogenous CCK released by various luminal stimulants drives the pancreatic protein secretion; 2) the release of CCK is confined to the foregut; and 3) PP concomitantly released by various intestinal stimulants may contribute to the control of pancreatic secretion induced by endogenous CCK.

Topics: Animals; Atropine; Cholecystokinin; Dogs; Food; Gastric Fistula; Meat; Oleic Acid; Oleic Acids; Pancreatic Fistula; Pancreatic Polypeptide; Perfusion; Sincalide; Somatostatin

Truncal vagotomy results in diminished pancreatic protein secretion in response to intraduodenal fat. This diminished secretion may be due, at least in part, to interruption of the vagal reflexes between the intestine and the pancreas that work independently of cholecystokinin (CCK). In five dogs with chronic pancreatic fistulas, plasma CCK concentrations and pancreatic protein secretion in response to an intestinal stimulant (intraduodenal oleate) and to two exogenous peptides (bombesin and CCK-33) were compared before and after bilateral truncal vagotomy. Vagotomy decreased integrated protein secretion by about 50% in response to intraduodenal oleate. In contrast, protein output in response to parenteral stimuli increased after vagotomy. Integrated output of CCK in response to intraduodenal oleate or to exogenous bombesin or CCK was not significantly affected by vagotomy, but release of pancreatic polypeptide was decreased significantly in response to all stimuli after truncal vagotomy. These data provide evidence that truncal vagotomy decreases pancreatic protein secretion in response to intestinal stimulants by interrupting enteropancreatic reflexes mediated by the vagus, while maintaining normal (or supranormal) sensitivity of the pancreas to endogenous and exogenous CCK.

Topics: Animals; Bombesin; Cholecystokinin; Dogs; Duodenum; Female; Male; Oleic Acid; Oleic Acids; Pancreas; Pancreatic Fistula; Pancreatic Polypeptide; Peptide Fragments; Proteins; Reflex; Sincalide; Stimulation, Chemical; Vagotomy; Vagus Nerve