gastrins and Fistula

Studies in animals demonstrate a gastric hormonal phase of pancreatic exocrine secretion. Endogenous or exogenous gastrin causes a marked elevation in the pancreatic enzymes and a lesser increase in the pancreatic volume and bicarbonate. It is possible that these "gastrin" effects may be the basis of a "cephalic" phase of pancreatic secretion. These observations have been only partially confirmed in human subjects with and without the Zollinger-Ellison syndrome. The physiologic importance of these ecbolic actions as well as a possible trophic effect remains to be elucidated.

Topics: Animals; Bicarbonates; Cats; Dogs; Eating; Fistula; Gastrins; Humans; Pancreas; Pentagastrin; Rats; Stomach; Trypsin; Vagotomy; Vagus Nerve; Zollinger-Ellison Syndrome

1. Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relative importance of luminal and neuronal mechanisms, by lesioning the antral innervation using benzalkonium chloride. 2. Benzalkonium chloride was applied to the serosa of the antrum in anaesthetized rats. In some animals, a stainless-steel cannula was also implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and histidine decarboxylase were measured by Northern blot. 3. Antral denervation was associated with gastric retention after fasting, and elevated plasma gastrin (28.4 +/- 7 pM compared with 7.6 +/- 1.0 pM in controls). When fasted control or denervated rats were refed, plasma gastrin increased 3-fold in both cases. A gastrin-releasing peptide antagonist inhibited the post-prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats. 4. In fasted, antrally denervated rats with a gastric fistula, basal gastric acid secretion was depressed 3-fold, and plasma gastrin concentrations were similar to controls. 5. Distension of the stomach with peptone via a barostat attached to the gastric cannula (5 cm H2O, 30 min), produced 3-fold increases in plasma gastrin in both control and denervated rats. However, distension with a non-nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a similar extent to peptone in denervated rats; distension with 50 mM HCl had no effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA abundances in the antrum were depressed by about 35% by antral denervation, but somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffected by antral denervation. 7. The data suggest that luminal nutrient releases gastrin in the rat, in vivo, via activation of antral neurons secreting gastrin-releasing peptide, and that the antral innervation normally inhibits G-cell responses to non-nutrient distension of the stomach. After antral denervation, gastric distension with a non-nutrient solution is an adequate stimulus for gastrin release.

Topics: Animals; Catheterization; Fasting; Fistula; Gastric Acid; Gastric Mucosa; Gastrins; Histidine Decarboxylase; Muscle Denervation; Muscle, Smooth; Postprandial Period; Pyloric Antrum; Radioimmunoassay; Rats; Rats, Wistar; RNA, Messenger; Somatostatin; Stomach

A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating insulin-stimulated acid output. On separate days, seven adult dogs with chronic gastric fistulas were pretreated i.v. with either 1) 7 mg of a gastrin monoclonal antibody (mAb 28.2); 2) 12.5 micrograms/kg atropine; 3) mAb 28.2 and atropine together; or 4) vehicle (0.1% canine serum albumin in 0.15 M NaCl). Thirty minutes later, acid secretion was stimulated by insulin (0.5 U/kg, i.v.), followed in 2 h by a 1-h infusion of histamine (40 micrograms/kg/h, i.v.). Acid output (mmol/15 min) in gastric effluent collected through the gastric fistula was determined by titration with 0.2 N NaOH to pH 7.0. Plasma gastrin was measured by radioimmunoassay. Plasma glucose was measured by a glucose oxidase method on an auto analyzer. Insulin induced a profound hypoglycemia (55 +/- 8 mg/dl) that coincided with a marked increase in acid output to 7.1 +/- 0.6 mmol/30 min by 45 min after injection. MAb 28.2 pretreatment and atropine pretreatment reduced insulin-stimulated acid outputs to 2.7 +/- 0.7 mmol/30 min and to 0.6 +/- 0.2 mmol/ 30 min, respectively. Acid output after combined pretreatment (0.5 +/- 0.2 mmol/30 min) was not significantly different than after atropine alone. Histamine-stimulated acid output (15.8 +/- 2.5 mmol/30 min) was not significantly reduced by any pretreatment. Insulin injection increased circulating gastrin concentrations to 32 +/- 7 fmol/ml, which was not significantly affected by atropine (39 +/- 9 fmol/ml). This study demonstrates that, in dogs, a significant part of insulin-stimulated acid secretion is mediated by circulating gastrin.

Topics: Animals; Antibodies, Monoclonal; Atropine; Dogs; Fistula; Gastric Acid; Gastric Mucosa; Gastrins; Insulin; Kinetics; Stomach; Time Factors

Nitric oxide (NO) was shown to mediate gastric hyperemia following secretory stimulation but its role in the control of gastric secretion has not been clarified. Secretory studies were carried out on conscious dogs with chronic gastric fistula, Heidenhain pouch and esophageal fistula, while changes in gastric blood flow were measured in the mucosa of Heidenhain pouuch by laser Doppler flowmetry. Plasma gastrin was determined by radioimmunoassay. Infusion of NG-nitro-L-arginine (L-NNA) (bolus i.v. injection of 2.5 mg/kg followed by infusion of 0.5 mg/kg/h), a potent inhibitor of nitric oxide synthase, failed to affect basal gastric secretion or plasma gastrin level but suppressed an increase of this secretion induced by sham-feeding, ordinary meat feeding or i.v. infusion of bombesin (0.5 microgram/kg/h), pentagastrin (4 micrograms/kg/h) or histamine (40 micrograms/kg/h). In tests with feeding and bombesin infusion, L-NNA caused a significant and dose-dependent reduction in plasma gastrin levels. The inhibition by L-NNA of gastric acid secretory response to pentagastrin, histamine or feeding was accompanied by a decline in blood flow. Addition of L-arginine (bolus i.v. dose of 50 mg/kg followed by infusion of 5 mg/kg/h) significantly attenuated the L-NNA induced inhibition of gastric secretion and the reduction in plasma gastrin response as well as in the fall of gastric blood flow. We conclude that endogenous nitric oxide affects the gastric secretion and that this effect is mediated, at least in part, by the changes in the gastrin release and gastric blood flow.

Topics: Animals; Arginine; Bombesin; Dogs; Eating; Fistula; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Infusions, Intravenous; Muscle, Smooth; Nitric Oxide; Nitroarginine; Pentagastrin; Regional Blood Flow; Stomach; Time Factors

Topics: Animals; Benzamides; Carbachol; Dogs; Fistula; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Keto Acids; Muscle, Smooth; Pentagastrin; Pentanoic Acids; Rats; Receptors, Cholecystokinin; Spiro Compounds; Stereoisomerism; Stomach

Topics: Animals; Cholecystokinin; Dogs; Duodenum; Esters; Fistula; Gabexate; Gastrin-Releasing Peptide; Gastrins; Guanidines; Immunoglobulins; Infusions, Intravenous; Pancreas; Peptides; Protease Inhibitors; Proteins

Basal, pentagastrin- and histamine-stimulated acid secretion were measured in gastric fistula rats treated with the H+/K(+)-ATPase inhibitor, omeprazole, and the H2-receptor antagonist, ranitidine. All doses of omeprazole (20, 30, 40, 80, 400 mumol/kg) and ranitidine (125, 187.5, 250, 375 mumol/kg) essentially abolished the basal acid output for various periods of time. Omeprazole, 80 mumol/kg, administered twice daily, reduced the 24-h basal acid secretion more effectively than did 400 mumol/kg given once daily. Four daily administrations of ranitidine reduced the 24-h basal acid output to a similar extent as omeprazole administered twice. Omeprazole (20, 80 mumol/kg) was more effective than ranitidine (125, 375 mumol/kg) in inhibiting acid secretion evoked by maximal doses of pentagastrin (650 nmol/kg per h) and histamine dihydrochloride (136 mumol/kg), whereas this difference was less pronounced for the inhibition of acid responses induced by a threshold dose (1.1 mumol/kg) of histamine. The inhibition evoked by omeprazole (80 mumol/kg x 2) and ranitidine (375 mumol/kg x 4) of basal and histamine (1.1 and 136 mumol/kg)-induced acid secretion was similar after 1 and 4 weeks of treatment. After the end of drug administration, the acid secretion induced by threshold doses of histamine was significantly elevated in the omeprazole-treated rats, whereas no significant hypersecretion of acid was seen during the recovery period in rats treated with ranitidine. Plasma gastrin concentrations were significantly elevated after 4 weeks of treatment with omeprazole but returned to pretreatment levels after 4 weeks of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Fistula; Gastric Acid; Gastrins; Histamine; In Vitro Techniques; Male; Omeprazole; Ranitidine; Rats; Rats, Inbred Strains; Stomach

Using conscious gastric fistula dogs, gastrin release stimulated by a 360-g meat-based solid meal was compared to that stimulated by two isocaloric (1 kcal/g), hypertonic (approximately 700 mosm/kg) nutrient liquids (Sustacal and Vivonex) and by two nonnutrient, hypotonic (60 mosm/kg) liquids (mannitol and coffee). Serum gastrin levels were measured at 15- to 30-min intervals over 120 min. Without a meal, serum gastrin levels remained stable. Effectiveness in stimulating gastrin release was coffee = mannitol less than Sustacal = Vivonex less than solid food; 2-hr integrated gastrin responses were 1.2, 2.6, 4.3, 5.6, and 12.2 ng/ml/min, respectively. The greater gastrin responses produced by nutrient liquids and meat meals could be explained by slower emptying and delayed acidification of gastric contents. We conclude that solid meals are preferable to liquid meals in studies of antral gastrin release.

Topics: Animals; Coffee; Dogs; Drinking; Eating; Fistula; Food; Food, Formulated; Gastric Mucosa; Gastrins; Mannitol; Osmolar Concentration; Stomach

1. In order to assess if proximal enterectomy induces changes in the function of the exocrine pancreas, the exocrine pancreas was studied 1 week, 4 weeks, and 6 months after 50 or 75% proximal small bowel resection. 2. One week after 50 and 75% proximal small bowel resections, basal pancreatic bicarbonate outputs, studied by means of an external pancreatic fistula in conscious rats, were increased significantly over control values by 43 and 78% respectively. Four weeks after a 75% resection, the bicarbonate output was still significantly higher in resected animals than in sham operated animals. 3. The increase of volume and bicarbonate of the basal pancreatic secretion coincided with a 4-fold increase in plasma secretin concentration 1 week after resection. Both increased pancreatic secretion and plasma secretin concentration were transient. 4. The pancreatic hypersecretion was specifically reversed to control values with an I.P. injection of jejunoileal mucosa homogenate. 5. Serum gastrin and somatostatin values in intestinal mucosa and pancreas were not changed 1 and 4 weeks after enterectomy compared with sham operated animals. 6. The weight of the pancreas and its content of DNA were unaltered by resection. Amylase and chymotrypsinogen per gram pancreatic tissue and per microgram DNA were reduced 4 weeks following resections as compared with sham operated rats. After 6 months, chymotrypsinogen appeared further reduced in resected animals. 7. It is concluded that extensive proximal enterectomy in rats produced early, transient and marked increases in basal pancreatic water and bicarbonate secretion and in plasma secretin due to the loss of jejunoileal inhibitor(s), and a selective decrease in certain enzymes in pancreatic tissue.

Topics: Animals; Bicarbonates; Fistula; Gastrins; Intestine, Small; Male; Pancreas; Rats; Rats, Inbred Strains; Secretin; Somatostatin

This study examines the effect of graded antral distension with acid (0.1 M HCl) or alkali (0.1 M NaHCO3) on pentagastrin-stimulated acid secretion in two groups of dogs. Group A consisted of six dogs provided with innervated antral pouch. In these dogs, the vagal branches to the fundus, as well as the extragastric vagal divisions (hepatic and celiac), were preserved. All of these animals had a gastric fistula in the main stomach, and in two a denervated fundic pouch or Heidenhain pouch was constructed in addition. Group B consisted of four dogs with an innervated antral pouch and gastric fistula. In this latter group, however, parietal cell vagotomy as well as extragastric vagotomy (division of the hepatic and celiac branches) was performed so that the only vagal communication was between the antrum and the CNS. Antral distension with acid caused significant inhibition of pentagastrin-stimulated acid secretion from both the gastric fistula and the Heidenhain pouch in Group A dogs. Antral acidification without distension did not inhibit. Alkaline antral distension in this group caused much less inhibition of acid secretion, but did cause significant increase in circulating immunoreactive gastrin. In Group B dogs, antral distension with neither acid nor alkali caused inhibition of pentagastrin-stimulated acid secretion, indicating that intact vagal supply to the oxyntic mucosa and/or to the extragastric abdominal organs is necessary for the inhibitory mechanism to operate. The results of this study suggest that: a) antral acidification per se does not inhibit pentagastrin-stimulated acid secretion; and b) antral distension with acid, and to a lesser extent with alkali, is inhibitory only if vagal innervation to the fundus and other abdominal viscera is preserved. The observations are compatible with the hypothesis that antral distension activates a neurohumoral inhibitory mechanism releasing the inhibitor reflexly from sites other than the antrum or CNS.

Topics: Animals; Bicarbonates; Dogs; Fistula; Gastric Juice; Gastrins; Hydrochloric Acid; Pentagastrin; Pressure; Pyloric Antrum; Stomach; Vagotomy

Topics: Animals; Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Ligation; Male; Pylorus; Rats; Reserpine; Stimulation, Chemical; Stomach; Time Factors; Vagotomy

Prostaglandin E1, while inhibiting gastric fistula and Heidenhain pouch acid output in the dog, did not inhibit gastrin released by acetylcholine irrigation of an isolated antral pouch independent of pH effect. Some increase in gastrin was noted to PGE1 against a background of calcium infusion and following a meal. This increase is presumably due to acid inhibition and to an increase in intraluminal pH.

Topics: Acetylcholine; Animals; Calcium; Dogs; Eating; Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Prostaglandins E; Stomach

This study was designed to determine whether cholecystokinin (CCK) plays a physiological role in the inhibition of gastric emptying. Physiological conditions were simulated by giving CCK by continuous intravenous infusion rather than by bolus injection, by using doses known to be distinctly submaximal for pancreatic protein secretion, and for gallbladder contraction, and by releasing endogenous CCK. The rate of gastric emptying was determined in 4 dogs with gastric fistulas by measuring the volume of fluid remaining in the stomach 10 min after instillation of 300 ml of 0.15 M NaCl. Rate of emptying was studied during intravenous infusion of saline (control) and of different doses of 98% pure CCK, commerically available 20% pure CCK, synthetic COOH-terminal octapeptide of CCK (OP-CCK), pentagastrin, and heptadecapeptide gastrin. The effect of endogenously released CCK was studied by measuring the rate of emptying of solutions in which different concentrations of tryptophan replaced equiosmolar amounts of NaCl. The d50's of 20% pure CCK (3 U kg minus-1 hr minus-1) and of OP-CCK (125 ng kg minus-1 hr minus-1) for inhibition of gastric emptying were about the same as their D50's for cholecystokinetic and pancreozyminic actions. By contrast, although both pentagastrin and heptadecapeptide gastrin inhibited gastric emptying, the doses required for this action were much higher than the D50's required for stimulation of gastric acid secretion. The effectiveness of OP-CCK indicates that inhibition of gastric emptying is attributable to CCK itself and not to an impurity in the CCK preparation. We have confirmed this directly by showing that pure CCK is a potent inhibitor of gastric emptying. Tryptophan also inhibited gastric emptying. In other dogs pancreatic protein secretion and gallbladder contraction were shown to be stimulated during the time tryptophan was inhibiting gastric emptying. This evidence supports the view that inhibition of gastric emptying is one of the physiological actions of CCK, but in the case of gastrin it must be regarded as a pharmacological action.

Topics: Animals; Cholecystokinin; Depression, Chemical; Dogs; Fistula; Gallbladder; Gastrins; Gastrointestinal Motility; Hormones; Infusions, Parenteral; Pancreas; Pentagastrin; Proteins; Sodium Chloride; Stomach; Time Factors; Tryptophan

The simultaneous effects of acute i.v. ethanol administration (1.3 gm./kg.) on pancreatic and gastric acid secretion was studied on dogs provided with chronic pancreatic and gastric fistulas (Thomas cannula) and subjected to a continuous i.v. injection of GIH secretin (0.5 CU./kg./hr.) and gastrin (Eurorga hog gastrin I-II, 6 gamma/kg./hr.). Acute i.v. ethanol inhibits the pancreatic secretion of protein (concentration and output) and stimulates gastric acid secretion. Experiments were repeated: 1. Superimposing an atropine infusion (1.0 mg./hr.) on the continuous hormonal perfusion. 2. After reserpine administration for 48 hours (0.10 mg./kg./24 hr.) Atropine abolished the ethanol-mediated inhibition of pancreatic protein secretion but did not prevent the alcohol-mediated gastric acid stimulation. Reserpine did not change the ethanol-mediated pancreatic inhibition. It is assumed that in nonalcoholic dogs, i.v. ethanol inhibits pancreatic secretion by an intermediate nervous mechanism and enhances gastric acid secretion by acting directly on the oxyntic cells. Reserpine induces a high plateau level of HCl secretion which obscures the ethanol-mediated excitatory influences on the oxyntic cells.

Topics: Animals; Atropine; Depression, Chemical; Dogs; Ethanol; Fistula; Gastric Juice; Gastrins; Gastrointestinal Hormones; Infusions, Parenteral; Pancreas; Reserpine; Stimulation, Chemical; Stomach; Swine

The Exalto-Mann-Williamson procedure produces peptic ulceration in nearly 100% of experimental animals but the mechanism is unknown. To investigate the possible hormonal role of the gastric acid hypersecretion seen after this procedure, we investigated preoperative and postoperative serum gastrin and secretin concentrations. There was no significant change in serum gastrin; however, serum secretin concentrations increased to 2 1/2 times the preoperatve value, most likely secondary to the enhanced secretion of gastric acid. These data do not suppport the theory that alterations in circulating secretin or gastrin levels are responsible for the gastric acid hypersecretion following the Exalto-Mann-Williamson operation.

Topics: Animals; Disease Models, Animal; Dogs; Fasting; Fistula; Gastric Juice; Gastrins; Gastroenterostomy; Jejunum; Peptic Ulcer; Secretin; Stomach

Topics: Animals; Dogs; Fistula; Gastric Juice; Gastrins; Hydrocortisone; Meat; Pyloric Antrum; Radioimmunoassay; Stimulation, Chemical; Stomach

Topics: Animals; Bicarbonates; Denervation; Dogs; Fistula; Gastric Juice; Gastrins; Pyloric Antrum; Pylorus; Radioimmunoassay; Reflex; Stomach; Vagus Nerve

Biological properties of pure natural human "big gastrin" (designated G-34 because it contains 34 amino acid residues) were compared with those of pure natural heptadecapeptide gastrins (G-17) from human and porcine sources. Radioimmunoassay inhibition curves indicated that G-17 was nearly 1.5 times more potent than G-34 with the antibody used in this study. This difference was confirmed by demonstration of increased immunoreactivity generated when G-34 was converted to G-17 by trypsinization. When infused intravenously into dogs with gastric fistulas and Heidenhain pouches in equimolar doses, G-34 produced slightly higher acid secretory responses than G-17. Responses to sulfated and nonsulfated forms were not significantly different, nor were responses to human and porcine G-17. During infusion of equimolar doses, steady-state serum gastrin concentrations were more than fivefold higher with G-34 than with G-17. The difference in steady-state blood concentrations could be accounted for by a corresponding difference in removal rates. The half times of the G-34 preparations averaged 15.8 min and the half times of the G-17 preparations averaged 3.2 min. The calculated spaces of distribution for G-17 and G-34 were similar, about 25% of body weight. When the increment in serum gastrin was plotted against acid secretory response it was found that nearly five times greater increments in molar concentrations of G-34 than of G-17 were required to produce the same rate of acid secretion. The potency of these two molecular forms of gastrin can be expressed in two different ways. Based on exogenous molar doses, the potencies of G-34 and G-17 were similar. However, based on molar increments in serum gastrin concentration, G-17 was approximately five times more potent than G-34. Hence, fractionation of these gastrin components may be important in estimation of the acid-stimulating action represented by total serum gastrin as measured by radio-immunoassay.

Topics: Animals; Antibodies; Antigen-Antibody Reactions; Antigens; Dogs; Fistula; Gastric Juice; Gastrins; Half-Life; Humans; Infusions, Parenteral; Peptides; Radioimmunoassay; Stomach; Sulfates; Swine; Time Factors; Trypsin

Topics: Animals; Atropine; Depression, Chemical; Diet; Dogs; Fistula; Gastric Juice; Gastrins; Hydrochloric Acid; Hydrogen-Ion Concentration; Insulin; Insulin Antagonists; Perfusion; Stimulation, Chemical; Stomach

Topics: Animals; Carnivora; Disease Models, Animal; Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Peptide Hydrolases; Stomach

Topics: Animals; Colon; Dogs; Fistula; Gastrins; Gastrointestinal Motility; Injections, Intravenous; Nutritional Physiological Phenomena; Peptides; Rectum

Topics: Animals; Fistula; Gastric Acidity Determination; Gastric Juice; Gastrins; Pepsin A; Rats