peptones and Gastric-Fistula

The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown.. To evaluate the antisecretory effects of S-0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants.. Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer.. In the Heidenhain pouch model, both intravenously administered and orally administered S-0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol-stimulated or histamine-stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non-selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S-0509 significantly inhibited pentagastrin-stimulated gastric acid secretion, yet the drug had no effect on carbachol-stimulated secretion.. S-0509 is a selective CCK-B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin-releasing substances, but does not inhibit histamine-stimulated and carbachol-stimulated acid secretion.

Topics: Animals; Atropine; Beer; Benzophenones; Carbachol; Dogs; Female; Gastric Acid; Gastric Fistula; Histamine; Male; Pentagastrin; Peptones; Phenylurea Compounds; Receptor, Cholecystokinin B; Receptors, Cholecystokinin

Neuropeptide Y (NPY), a centrally located neurotransmitter, is known to increase appetite in fasted and satiated animals. In addition to evaluating NPY's effect on eating behavior, this study was intended to determine whether intracerebroventricular (ICV) NPY would have an effect on canine gastric and pancreatic secretion.. Four dogs were prepared with cerebroventricular guides and gastric and pancreatic fistulas. ICV and intravenous NPY was administered during intragastric titration of a glucose and peptone meal. During this study, gastric and pancreatic secretion was measured, as well as insulin levels and pancreatic polypeptide (PP). An additional set of four dogs were prepared with esophageal fistulas and cerebroventricular guides, and the effect of ICV NPY on sham feeding was studied.. ICV NPY significantly increased sham feeding, meal-stimulated gastric and pancreatic secretion, basal gastric acid, pancreatic bicarbonate, insulin levels, and PP. Vagotomy blocked the effect of ICV NPY on gastric acid secretion in a urethane-anesthetized rat model with acute gastric fistula.. ICV NPY increased sham feeding, gastric and pancreatic secretion, insulin levels, and PP in the dogs. NPY's effect on gastric secretion was blocked by vagotomy in a rat model. NPY should be considered a candidate mediator of cephalic phase secretion.

Topics: Analysis of Variance; Animals; Bicarbonates; Disease Models, Animal; Dogs; Eating; Female; Gastric Acid; Gastric Acidity Determination; Gastric Fistula; Gastric Mucosa; Glucose; Injections, Intravenous; Injections, Intraventricular; Insulin; Insulin Secretion; Male; Neuropeptide Y; Pancreas; Pancreatic Polypeptide; Peptones; Rats; Rats, Sprague-Dawley; Vagus Nerve

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

In conscious gastric fistula rats, gastric distension with saline to a pressure of 7 cm caused a threefold reduction of basal gastric acid secretion. Distension with 6.25% peptone solution to the same pressure doubled basal acid secretion. The saline distension-induced inhibition was abolished by guanethidine and markedly reduced by propranolol; phentolamine was ineffective. The response to peptone was unaffected by guanethidine. The results suggest that in the rat, gastric distension at physiological pressures inhibits acid secretion by a beta-adrenergic reflex. The inhibition can be masked by concurrent chemical stimulation of the gastric mucosa by the digestion products of food.

Topics: Animals; Gastric Acid; Gastric Fistula; Gastric Mucosa; Guanethidine; Hydrostatic Pressure; Kinetics; Male; Peptones; Phentolamine; Propranolol; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Sodium Chloride; Solutions

Previous studies have questioned the physiological role of gastric inhibitory peptide in inhibiting gastric acid secretion. The present study was designed to examine and compare peptone meal-stimulated gastric acid secretion in dogs after intravenous infusion of rabbit serum containing antibodies to gastric inhibitory peptide or normal rabbit serum (as control). Five dogs were prepared with gastric fistulas. Basal acid output was collected for 90 min through the gastric fistula. After 30 min of basal acid output collection, either rabbit serum containing antibodies to gastric inhibitory peptide or normal control rabbit serum (0.1 ml/kg) was infused intravenously over 1 min. After the basal acid output collection, a 10% peptone meal was infused into the stomach. Gastric acid output was measured by intragastric titration (pH 5.0) for 60 min. Peripheral venous plasma was collected for measurement of gastrin and gastric inhibitory peptide and for binding of endogenous plasma gastric inhibitory peptide by administered antibodies to gastric inhibitory peptide before and at 2, 5, 10, 15, 30, 60, 90, and 120 min after the meal. After intravenous administration of antibodies to gastric inhibitory peptide, 98% +/- 3% (SEM) of endogenous plasma gastric inhibitory peptide was bound by administered antibodies to gastric inhibitory peptide. No binding of endogenous plasma gastric inhibitory peptide was detected after infusion of normal rabbit serum. In dogs receiving intravenous antibodies to gastric inhibitory peptide, both peptone-stimulated gastric acid output and integrated gastrin release responses were increased when compared with dogs receiving normal rabbit serum. With infusion of antibodies to gastric inhibitory peptide, there was a high degree of correlation between the increase in gastric acid output and the increase in integrated gastrin response (r = 0.900, p less than 0.04) that followed the peptone meal. This study, using antibodies to bind endogenous gastric inhibitory peptide, demonstrates the capacity of circulating gastric inhibitory peptide to inhibit meal-stimulated gastric acid secretion. Furthermore, these results support the conclusion that this enterogastrone effect of gastric inhibitory peptide is due, at least in part, to inhibition of gastrin release.

Topics: Animals; Antibodies; Dogs; Female; Gastric Acid; Gastric Fistula; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Male; Peptones; Radioimmunoassay

Vasoactive inhibitory peptide (VIP) and secretin were compared in regard to the stimulation of pancreatic bicarbonate secretion and the augmentation of pancreatic response to caerulein or a peptone meal in chronic gastric and pancreatic fistula dogs. Dose-response analysis showed that maximal bicarbonate response to VIP was about 17% of that to secretin. Both caerulein and endogenous cholecystokinin, released by a peptone meal, clearly potentiated pancreatic bicarbonate response to VIP in a manner similar to secretin. The interactions of these two peptides showed that VIP is a potent inhibitor of secretin-induced pancreatic secretion. From the dose-response curves to secretin alone and secretin plus VIP, Michaelis-Menten analysis showed typical competitive inhibition, which indicates that VIP and secretin share a common receptor site.

Topics: Amylases; Animals; Bicarbonates; Ceruletide; Cholecystokinin; Depression, Chemical; Dogs; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Gastric Fistula; Gastrointestinal Hormones; Infusions, Parenteral; Kinetics; Pancreas; Pancreatic Fistula; Pancreatic Juice; Peptides; Peptones; Proteins; Secretin

Topics: Acetylcholine; Animals; Bicarbonates; Dogs; Ethanol; Gastric Fistula; Gastric Juice; Gastrins; Glycine; Histamine; Hydrogen-Ion Concentration; Injections, Intravenous; Liver Extracts; Peptones; Sodium Chloride; Stomach

Topics: Amylases; Animals; Dogs; Gastric Fistula; Hydrochloric Acid; Intestinal Fistula; Lipase; Methantheline; Pancreas; Pancreatic Juice; Parasympatholytics; Peptones; Pharmacology; Quaternary Ammonium Compounds; Research; Secretin; Soaps