gastrins and Gastric-Fistula

This investigation examined the effect of rioprostil, a primary alcohol prostaglandin E1 analog, on betazole-stimulated gastric acid secretion and on basal and food-stimulated (postprandial) serum gastrin levels in gastric fistula dogs. Rioprostil inhibited betazole-stimulated gastric acid secretion with an ED50 of 16 (10-24) micrograms/kg, intragastrically. A near-maximal gastric antisecretory dose (100 micrograms/kg, intragastrically) had no effect on basal serum gastrin levels but significantly attenuated the rapid rise in serum gastrin which follows feeding, a result different from that reported for other prostaglandin E1 analogs. A nonantisecretory dose of rioprostil (1.0 micrograms/kg, intragastrically) also attenuated the rise in postprandial serum gastrin. An antigastrin effect using a nonantisecretory dose of an antiulcer agent has not been reported previously and may indicate that rioprostil has a direct inhibitory effect on secretion of gastrin. The ability of rioprostil to inhibit gastric acid secretion and decrease postprandial peak serum gastrin levels, coupled with previously established cytoprotective efficacy, makes it an attractive clinical candidate for the treatment and prevention of peptic ulcer disease.

Topics: Animals; Anti-Ulcer Agents; Depression, Chemical; Dogs; Female; Gastric Acid; Gastric Fistula; Gastrins; Gastrointestinal Contents; Peptic Ulcer; Prostaglandins E; Radioimmunoassay; Rioprostil

Topics: 2,2'-Dipyridyl; Animals; Anura; Catecholamines; Cats; Dogs; Gastric Fistula; Gastric Mucosa; Gastrins; Gastrointestinal Agents; Gastrointestinal Hormones; Guinea Pigs; Histamine H1 Antagonists; Histamine Release; Ligation; Pepsin A; Peptic Ulcer; Proglumide; Prostaglandins; Pylorus; Quaternary Ammonium Compounds; Rats; Stomach; Sympatholytics; Thiazoles; Thioacetamide

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

Wistar Kyoto (WKY) rats are more susceptible to stress-evoked ulcerations than Sprague-Dawley (SPD) rats. We have already demonstrated that gastrin cells are more active and ghrelin cells less active in WKY rats than in SPD rats. The purpose of this study was to compare endocrine cell activity and gastric acid output in WKY and SPD rats.. Gastric acid output was determined in conscious rats with gastric fistula. Plasma gastrin and ghrelin levels were measured after an overnight fast. Acid secretagogues (gastrin, histamine and carbachol) were given by continuous subcutaneous infusion.. The volume of gastric juice, and the acidity and acid output were all significantly lower (p <0.05) in fasted WKY rats than in fasted SPD rats. Gastrin evoked a 4-fold (p <0.01) and 3-fold (p <0.05) increase in gastric acid output in SPD rats and WKY rats, respectively. Histamine raised the acid output 1.6-fold in SPD rats (p=0.06) and 3-fold in WKY rats (p <0.05), while carbachol failed to affect the acid output (weak increase, p >0.05). Fasting plasma ghrelin levels were 2-fold higher in SPD rats than in WKY rats (p <0.01) while fasting gastrin levels were 10-fold higher in WKY rats than in SPD rats (p <0.05). Neither the parietal-cell density nor the oxyntic mucosal thickness differed between the two strains.. The results of the present study suggest that a high gastrin cell activity in WKY rats is secondary to a low gastric acidity. Whether the high gastrin cell activity is linked to susceptibility to stress ulcer in WKY rats warrants further investigation.

Topics: Animals; Anxiety; Basal Metabolism; Carbachol; Female; Gastric Acid; Gastric Fistula; Gastrin-Secreting Cells; Gastrins; Ghrelin; Histamine; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; Stimulation, Chemical

To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.. A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed.. All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001).. pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.

Topics: Animals; Capsule Endoscopes; Capsule Endoscopy; Disease Models, Animal; Esomeprazole; Gastric Acid; Gastric Acidity Determination; Gastric Fistula; Gastric Mucosa; Gastrins; Gastrointestinal Agents; Gastrointestinal Hormones; Ghrelin; Hydrogen-Ion Concentration; Male; Monitoring, Ambulatory; Pentagastrin; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Somatostatin; Telemetry; Time Factors

The effects of a new benzimidazole derivative, ME3407 (n-butyl-2-(thiazolo-[5,4-b]pyrid-2-yl) sulfinylacetate, CAS 133903-90-9), on gastric acid secretion and gastric and duodenal ulcers in rats were examined. ME3407, given orally, inhibited dose-dependently (0.3-30 mg/kg) the incidence of gastric lesions such as Shay ulcers, and water-immersion stress-, acetylsalicylic acid (ASA)- and histamine-induced erosions. In addition, ME3407 showed marked therapeutic effect on HCl- and ASA-induced lesions. In the lumen-perfused rats, oral administration of ME3407 inhibited dose-dependently (1-100 mg/kg) gastric acid secretion induced by histamine and tetragastrin with ED50 values of 3.02 and 3.37 mg/kg, respectively. Oral administration of ME3407 at a dose of 30 mg/kg also inhibited the elevation of serum gastrin level. The development of duodenal ulcers caused by mepirizole and systeamine was also potently inhibited by ME3407 at an oral dose of 0.1-30 mg/kg. However, when given at 30 mg/kg intraduodenally, subcutaneously or intravenously, ME3407 did not inhibit these acutely induced gastric elosion and acid output. ME3407 was not detected in the serum upon oral administration. These results indicated that ME3407 was active only by oral administration, and exerts direct action on the ulcers and acid secretion from the gastric membrane.

Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Aspirin; Benzimidazoles; Cysteamine; Duodenal Ulcer; Epirizole; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine; Immersion; Indomethacin; Male; Pepsin A; Pylorus; Pyridines; Rats; Stomach Ulcer; Thiazoles

Gastrimmune is an immunogenic form of gastrin. It raises in situ antibodies against two proliferative forms of gastrin: amidated and glycine-extended gastrin-17. It has been shown to have a therapeutic action in several in vivo tumour models. Following immunization, due to the complex equilibrium that exists between the antibodies and gastrin, it is not technically feasible to assay for free gastrin.. To determine the effect of Gastrimmune-induced antigastrin antibodies on acid secretion.. A rat gastric fistula model was used. Animals (six per group) were immunized with a control immunogen or ascending doses of Gastrimmune. Acid output was measured following infusion of increasing doses of gastrin-17 and pentagastrin.. Gastrimmune-induced antibodies significantly reduced gastrin-17-stimulated acid output compared to control animals (Gastrimmune at 200 microg/rat vs. control; acid output following 30 ng gastrin-17, 0.01 vs. 0.16, P < 0.001; following 120 ng gastrin-17, 0.022 vs. 0.29, P < 0.001).. Gastrimmune significantly inhibits gastrin-17-stimulated acid output. This biological assay suggests that the antigastrin antibodies effectively bind gastrin-17. In addition to its use as an antineoplastic agent, Gastrimmune may have a role as an acid-decreasing agent in oesophagogastric pathology.

Topics: Animals; Antibodies; Cancer Vaccines; Diphtheria Toxoid; Disease Models, Animal; Female; Gastric Acid; Gastric Fistula; Gastrins; Gastrointestinal Agents; Immunization; Male; Pentagastrin; Rats; Rats, Wistar

By mobilizing histamine in response to gastrin, the ECL cells in the oxyntic mucosa play a key role in the control of the parietal cells and hence of gastric acid secretion. General anaesthesia suppresses basal and gastrin- and histamine-stimulated acid secretion. The present study examines if the effect of anaesthesia on basal and gastrin-stimulated acid secretion is associated with suppressed ECL-cell histamine secretion. A microdialysis probe was implanted in the submucosa of the ventral aspect of the acid-producing part of the stomach (32 rats). Three days later, ECL-cell histamine mobilization was monitored 2 h before and 4 h after the start of intravenous infusion of gastrin (5 nmol kg(-1) h(-1)). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents were given 1 h before the start of the experiments by intraperitoneal injection: chloral hydrate (300 mg kg(-1)), pentobarbitone (40 mg kg(-1)), urethane (1.5 g kg(-1)) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7.5 mg kg(-1)). In a parallel series of experiments, basal- and gastrin-induced acid secretion was monitored in six conscious and 25 anaesthetized (see above) chronic gastric fistula rats. All anaesthetic agents lowered gastrin-stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl/midazolam was an exception). Anaesthesia reduced gastrin-stimulated but not basal histamine release by 55 - 80%. The reduction in gastrin-induced acid response (70 - 95%) was strongly correlated to the reduction in gastrin-induced histamine mobilization. The correlation is in line with the view that the reduced acid response to gastrin reflects impaired histamine mobilization. Rat stomach ECL cells were purified by counter-flow elutriation. Gastrin-evoked histamine mobilization from the isolated ECL cells was determined in the absence or presence of anaesthetic agents in the medium. With the exception of urethane, they inhibited gastrin-evoked histamine secretion dose-dependently, indicating a direct effect on the ECL cells. Anaesthetized rats are widely used to study acid secretion and ECL-cell histamine release. The present results illustrate the short-comings of such an approach in that a number of anaesthetic agents were found to impair not only acid secretion but also the secretion of ECL-cell histamine - some acting in a direct manner.

Topics: Analysis of Variance; Anesthesia; Anesthetics; Anesthetics, Intravenous; Animals; Butyrophenones; Cells, Cultured; Chloral Hydrate; Consciousness; Dose-Response Relationship, Drug; Fentanyl; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine Release; Infusions, Intravenous; Male; Microdialysis; Midazolam; Pentobarbital; Rats; Rats, Sprague-Dawley; Stomach; Urethane

The antigastrinic, antisecretory and antiulcer activities of CR 2945, (R)-1-naphthalenepropanoic acid,beta-[2-[[2-(8-azaspiro[4.5]dec-8-yl-carbonyl)-4,6-dimethylph enyl] amino]-2-oxoethyl], were investigated in vitro and in vivo in rats and cats. Its activities were compared with those of two gastrin/CCK(B) receptor antagonists, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl)-N'-(3-methylphenyl)urea and CAM-1028 (4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[[1,7,7-trimethylbicyclo [2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino -4-oxo-[1S-1alpha,2beta[S'(S')4alpha]]-butanoate -N-methyl-D-glucamine), of the histamine H2 receptor antagonist, ranitidine, and the proton pump inhibitor, omeprazole. Cytosolic Ca2+ elevation in rabbit parietal cells induced by gastrin (50 nM) was blocked by CR 2945 with an IC50 value of 5.9 nM. CAM-1028 and L-365,260 showed similar activity. CR 2945 antagonized pentagastrin-stimulated gastric acid secretion in rats (ED50 = 1.3 mg kg(-1) i.v. and 2.7 mg kg(-1) i.d.) and cats (1.6 mg kg(-1) i.v.). CR 2945 was slightly less potent than the reference compounds after i.v. administration, whereas after intraduodenal (i.d.) administration, it was more potent than both ranitidine and omeprazole. In the rat, the gastrin antagonism exhibited by CR 2945 was reversible and competitive, with a pA2 value of 7.33. CR 2945 had specific antigastrin activity, as it was unable to antagonize the gastric acid secretion stimulated by histamine or carbachol in rats up to the dose of 30 mg kg(-1). CR 2945 was about as efficacious as ranitidine against the indomethacin- and ethanol-induced gastric ulcers and the cysteamine-induced duodenal ulcer in rats. On the contrary, L-365,260 was only slightly effective. These results suggest that CR 2945 might be a promising compound for the therapy of acid-related disorders, and that its clinical use could help clarify the therapeutic potential of gastrin/CCK(B) receptor antagonists in the gut.

Topics: Animals; Anti-Anxiety Agents; Anti-Ulcer Agents; Benzodiazepines; Benzodiazepinones; Calcium; Cats; Chronic Disease; Cysteamine; Dose-Response Relationship, Drug; Ethanol; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Indomethacin; Male; Omeprazole; Parietal Cells, Gastric; Pentagastrin; Perfusion; Phenylurea Compounds; Rabbits; Ranitidine; Rats; Receptors, Cholecystokinin; Stomach; Stomach Ulcer

Gastrin is a physiologically important secretagogue. It is thought to stimulate parietal cells indirectly by mobilizing histamine from enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin stimulates the secretory activity and growth of the ECL cells via an action on cholecystokinin-B/gastrin receptors. Acute cholecystokinin-B/gastrin receptor blockade is known to inhibit gastrin-stimulated acid secretion but whether sustained cholecystokinin-B/gastrin receptor blockade will impair basal, gastrin- and histamine-stimulated acid secretion remains uncertain. The present study was designed to study the effect of long-term (4 weeks) cholecystokinin-B/gastrin receptor blockade on basal and stimulated acid secretion in conscious rats. The selective cholecystokinin-B/gastrin receptor antagonist YM022 (3 mumol.kg-1.hr-1) was given to gastric fistula rats by continuous subcutaneous infusion via osmotic minipumps for various times from 2 hr to 4 weeks. Basal, gastrin- and histamine-stimulated acid secretion were examined during and after cessation of treatment. Basal and histamine-stimulated acid secretion was not affected by YM022 during the 4 week period of administration, whereas gastrin-induced acid secretion was inhibited. YM022 induced hypergastrinaemia in freely fed rats but did not affect the serum gastrin level in fasted rats. The serum gastrin concentration and gastrin-induced acid secretion returned to control levels 3-7 days after termination of YM022 administration.

Topics: Animals; Benzodiazepines; Cholecystokinin; Gastric Acid; Gastric Fistula; Gastrins; Histamine; Hormone Antagonists; Male; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin

We investigated the effects of the novel CCKB/gastrin antagonist YM022 on gastric acid secretion in vivo and in vitro, compared to CI-988 and L365,260 as reference antagonists. In the anaesthetized rat, pentagastrin-induced stimulation of gastric acid secretion was dose-dependently and up to 100% inhibited by i.v. administration of YM022 with an ID50 of 0.009 +/- 0.0006 mumol/kg h in comparison to 0.6 +/- 0.03 and 3.40 +/- 0.05 mumol/kg h for CI-988 and L-365,260, respectively. In the gastric fistula cat, i.v. administration of YM022 produced a similar inhibitory effect with an ID50 of 0.02 mumol/kg in comparison to 1.6 and 2.5 mumol/kg for CI-988 and L-365,260, respectively. Furthermore, bolus injection of 0.6 mumol/kg YM022 produced 100% inhibition within 30 min and 85% inhibition was still observed after 3 h. In the isolated rabbit gastric glands, CCK8-stimulated 14C-aminopyrine uptake was inhibited according to the following rank order of potency: YM022 (IC50 = 0.0012 microM) > > CI-988 (IC50 = 0.2 microM) > > L365,260 (IC50 = 2.8 microM). Unlike with L365,260, no influence of CI-988 and YM022 on histamine-stimulated acid output was shown in this study. Thus, YM022 is a highly potent and selective gastric CCKB/gastrin receptor antagonist and has a long-lasting inhibitory effect on gastric acid secretion.

Topics: Aminopyrine; Animals; Benzodiazepines; Benzodiazepinones; Cats; Cholecystokinin; Dose-Response Relationship, Drug; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Hormone Antagonists; Indoles; Male; Meglumine; Phenylurea Compounds; Rabbits; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Receptors, Cholecystokinin

We determined the relative contributions of endogenous gastrin, histamine and cholinergic tone to basal acid secretion in chronic fistula rats. Results were compared with those for acid secretion in pylorus-ligated rats. In chronic fistula rats, YM022 ¿(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1 H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea¿ dose-dependently inhibited pentagastrin-stimulated acid secretion and abolished this secretion at 1 mumol/kg, s.c., but did not affect histamine- and carbachol-induced acid secretion even at 10 mumol/kg. In contrast, famotidine at 1 mumol/kg completely inhibited not only the acid secretion induced by histamine but also those by pentagastrin and carbachol. Furthermore, atropine abolished carbachol- and pentagastrin-stimulated acid secretion and significantly suppressed histamine-stimulated acid secretion at 0.1 mumol/kg. YM022 dose-dependently inhibited basal acid secretion. The YM022 dosage required to inhibit basal acid secretion is consistent with that required to suppress pentagastrin-induced acid secretion. Famotidine (1 mumol/kg) and atropine (0.1 mumol/kg) also abolished basal acid secretion. In pylorus-ligated rats, YM022 inhibited acid secretion in a dose-dependent manner; the inhibition at 1 mumol/kg, i.v. was 65%. No additional effect was observed when rats were dosed at 30 mumol/kg. Famotidine partially inhibited acid secretion in these rats, whereas atropine abolished this secretion. These results indicate that the major part of basal acid secretion in rats is attributable to endogenous gastrin via histamine- and cholinergic tone-dependent pathways. Moreover, pylorus ligation reduces the relative contribution of gastrin to acid secretion due to the activation of cholinergic tone.

Topics: Animals; Atropine; Benzodiazepines; Chronic Disease; Famotidine; Gastric Acid; Gastric Fistula; Gastrins; Histamine; Ligation; Male; Parasympathetic Nervous System; Pylorus; Rats; Rats, Sprague-Dawley

Histamine is thought to play a central role in the regulation of gastric acid secretion. In the rat oxyntic mucosa most of the histamine is synthesized and stored in enterochromaffin-like (ECL) cells, and the rest resides in mast cells. The present study examines the role of ECL-cell histamine in the control of acid secretion in the intact, conscious rat.. Rats were treated with alpha-fluoromethylhistidine (alpha-FMH) to inhibit histamine synthesis. alpha-FMH was given by continuous subcutaneous infusion (3 mg/kg/h) for up to 9 days. An additional oral dose of alpha-FMH (50 mg/kg) was given 2 h before each acid secretion test. Acid secretion was studied in pylorus-ligated rats and in chronic gastric fistula rats stimulated with histamine, gastrin-17, or insulin after 2-6 days of alpha-FMH infusion.. Treatment with alpha-FMH lowered oxyntic mucosal histamine synthesis by 80%. From previous observations this is thought to reflect depletion of histamine from the ECL cells. The remaining 20% resides in mucosal and submucosal mast cells, which seem to be resistant to alpha-FMH. Basal acid secretion was inhibited by more than 60% after alpha-FMH treatment and by more than 80% by ranitidine. Histamine-stimulated secretion was unaffected by alpha-FMH and abolished by the histamine H2-receptor antagonist ranitidine. The acid response to gastrin-17 was almost abolished in histamine-depleted rats and abolished by ranitidine. Vagally induced acid secretion (provoked by the injection of insulin or by pylorus ligation) was unaffected by alpha-FMH treatment but abolished by ranitidine and by the muscarinic M1-receptor antagonist pirenzepine.. The results suggest that gastrin stimulates acid secretion by releasing histamine from ECL cells. Vagally induced acid secretion is also dependent on a histaminergic pathway but not on ECL-cell histamine.

Topics: Animals; Disease Models, Animal; Enterochromaffin Cells; Enzyme Inhibitors; Female; Gastric Acid; Gastric Fistula; Gastrins; Histamine; Methylhistidines; Parietal Cells, Gastric; Rats; Rats, Sprague-Dawley

The purpose of this study was to analyze the relative part of the cephalic phase in the gastric secretory and circulating gastrin responses to meals of variable composition and palatability in dogs. Meal palatability was quantified by measuring the ingestion rate of a fixed amount of food. By progressively increasing the amount of carbohydrates or lipids added to a normal meat meal, it was possible to obtain eleven meals of progressively decreasing ingestion rate. When were offered as sham-feeding these eleven meals in dogs fitted with a cervical esophagostomy and a gastric fistula, gastric acid response decreased only after meals of very small ingestion rates. Moreover, neither gastrin, nor gastric pepsin responses changed significantly with ingestion rate of the sham-fed meals. By subtracting the response to sham-fed meals from the response to real meals of identical composition, it was possible to calculate the non-cephalic part of gastric responses. The non-cephalic part of gastric acid secretion and of circulating gastrin was significantly correlated to calorie intake; the slope of the best fitting regression line was greater after lipid meals than after carbohydrate meals. The non-cephalic part of pepsin secretion was very small, if any, and its level was not correlated to the amount of ingested calories. This work suggests that palatability has very little influence on gastric secretion control in dogs.

Topics: Animals; Dogs; Energy Intake; Esophagostomy; Gastric Acid; Gastric Fistula; Gastrins; Pepsin A

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.

Topics: Animals; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine; Histamine Release; Histidine Decarboxylase; Male; Rats; Rats, Wistar; Somatostatin; Urinary Bladder Fistula

The effect of (R)alpha-methylhistamine (MH) and thioperamide (selective agonist and antagonist respectively of histamine H3 receptors) was examined in conscious gastric fistula dogs to investigate the role of histamine H3 receptors in the control of basal and stimulated gastric acid secretion. Intravenous infusion of MH at 0.3 and 0.6 mumol/kg/h caused a significant reduction of the 2-deoxy-D-glucose (2-DG)-stimulated acid output, maximal inhibition being 60%. The inhibitory effect of MH was counteracted by thioperamide (0.1 mumol/kg/h), which, by itself, did not modify the 2-DG-induced acid secretion. The increase in plasma gastrin levels induced by 2-DG was not significantly affected either by MH or by thioperamide. Under basal conditions MH (0.3 mumol/kg/h) did not induce any significant change in acid secretion and in plasma gastrin levels; by contrast, thioperamide (0.1 mumol/kg/h) produced a significant increase both in acid output and in plasma gastrin. These results suggest that activation of H3 receptors can exert a negative control in stimulated acid secretion in conscious dogs, when cholinergic pathways to acid secretion are activated by 2-DG; moreover, the slight, but significant, stimulatory effect of thioperamide on basal acid output and basal plasma gastrin may be suggestive for a tonic inhibitory role of H3 receptors in the regulation of basal acid secretion, however, a nonspecific effect of this drug cannot be excluded.

Topics: Animals; Deoxyglucose; Dogs; Female; Gastric Acid; Gastric Fistula; Gastrins; Male; Methylhistamines; Piperidines; Receptors, Histamine; Receptors, Histamine H3

The effects of esaprazole, a novel antiulcer drug, on gastric acid secretion and plasma gastrin levels were investigated in dogs provided with a gastric fistula or Heidenhain pouch. Esaprazole affected in a different extent the tests performed on dogs with a gastric fistula. The greatest inhibitory effect was obtained against 2-deoxy-D-glucose-induced acid output and gastrin release. An intermediate inhibition by esaprazole was detected on bethanechol-evoked secretion, and the lowest activity was found versus histamine-stimulated secretion. All these responses were strongly inhibited by the antimuscarinic drug pirenzepine used as reference drug. Moreover, both esaprazole and pirenzepine prevented the acid secretory response to a test meal in dogs with a Heidenhain pouch, without significantly affecting plasma gastrin levels. The present results suggest that the depressant action of esaprazole on gastric secretion depends on its peripheral anticholinergic activity, consisting of a partial blockade of acid output and a main reduction of vagally mediated gastrin release. On the basis of these findings, the antiulcer activity of esaprazole might be in part ascribed to its inhibitory effects on gastric secretion.

Topics: Animals; Anti-Ulcer Agents; Dogs; Female; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Guinea Pigs; Ileum; In Vitro Techniques; Male; Piperazines; Radioimmunoassay; Rats; Rats, Wistar

The antigastrinic activity, in vivo, of CR 2194 (R-4-(3-chlorobenzamido)-5-(8-azaspiro[4.5]decan-8-yl) -5-oxo pentanoic acid) was assessed in various animal species. CR 2194 antagonized pentagastrin-stimulated gastric acid secretion in the rat (ID50 = 11 mg/kg i.v.), dog (ID50 = 5.9 mk/kg i.v. or 28.8 mg/kg os) and cat (ID50 = 15.5 mg/kg i.v.). CR 2194, in the cat, inhibited both competitively and non-competitively the gastric acid secretion stimulated with increased doses of pentagastrin, with a pA2 of 4.89. In the rat and in the dog the antagonism seemed to be non-competitive and the respective pD'2 calculated were 4.54 and 4.42. The interaction of CR 2194 with the gastrin receptors appeared reversible, as demonstrated by the return to normal values of the acid output after the conclusion of the i.v. infusion, during pentagastrin continuous stimulation in the dog. The antigastrin activity was specific: CR 2194 was unable to antagonize the gastric acid secretion stimulated by carbachol or histamine in the rat up to the dose of 100 mg/kg. CR 2194 was effective to antagonize the gastric acid secretion stimulated by gastrin release after meal ingestion in the Heidenhain pouch dog model. The ID50 calculated was 2.89 mg/kg after oral administration. All these characteristics make CR 2194 an important compound in the investigation of the biological effects of gastrin and a potential agent for diagnostic or therapeutic use.

Topics: Animals; Binding, Competitive; Cats; Dogs; Eating; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Keto Acids; Male; Pentagastrin; Perfusion; Rats; Rats, Sprague-Dawley; Spiro Compounds

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

Fasting serum gastrin levels greater than 1000 pg/ml are said to establish the diagnosis of gastrinoma in a patient with peptic ulcer disease. The authors observed a patient with recurrent peptic ulcer disease, diarrhea, and a fasting serum gastrin of 1044 pg/ml who had a gastrocolic fistula, not the Zollinger-Ellison syndrome. The provocative tests of gastrin secretion, including secretin infusion and standard meal test, were helpful in ruling out a gastrinoma. This is the first reported association of gastrocolic fistula and hypergastrinemia. The patient demonstrates that the differential diagnosis of markedly elevated serum gastrin should be expanded to include gastrocolic fistula.

Topics: Adult; Colonic Diseases; Diagnosis, Differential; Female; Gastric Fistula; Gastrins; Humans; Intestinal Fistula; Stomach Ulcer; Zollinger-Ellison Syndrome

We studied the acute effect of transthoracic truncal vagotomy or sham vagotomy (control) on fasting serum gastrin concentrations in 22 gastric fistula dogs. A significant (p less than 0.05) decrease in serum gastrin concentration was detectable within 2.5 minutes after truncal vagotomy, and by 120 minutes serum gastrin has decreased to 15 +/- 1 pg/mL in the vagotomy group compared to 28 +/- 3 pg/mL in the control group (p less than 0.001). However by 24 hours after vagotomy, when maximal acid output was reduced by approximately 50%, fasting serum gastrin had increased nearly twofold above control levels in the vagotomy group (p = 0.06) and this increase persisted at day 7 (p less than 0.05). Thus truncal vagotomy had a biphasic effect on serum gastrin concentrations in dogs (acute inhibition followed by stimulation). While the mechanism for the acute fall in gastrin is probably an acute denervation of postganglionic neurons that innervate gastrin cells, the mechanism for the subsequent rise in serum gastrin remains uncertain.

Topics: Animals; Dogs; Gastric Acid; Gastric Fistula; Gastrins; Time Factors; Vagotomy, Truncal

To stimulate peripheral gamma-aminobutyric acid (GABA) receptors, GABA, which does not cross the blood-brain barrier, was administered to dogs with vagally innervated gastric fistulas at intravenous doses of 0, 0.66, 2, 6, 18, and 54 micrograms.kg-1.min-1. Mean gastric acid output increased from zero basally to 3.0 +/- 1.4 mmol/h during infusion of 54 micrograms.kg-1.min-1 GABA. Plasma somatostatin-like immunoreactivity decreased significantly below basal levels during infusion of 54 micrograms.kg-1.min-1 GABA (P less than 0.05). To stimulate central nervous system GABA receptors as well as peripheral GABA receptors, progabide, a GABA-receptor agonist, which readily crosses the blood-brain barrier, was injected intravenously. Mean acid output was 3.5 +/- 1.3 mmol/h after 20 mg/kg progabide and 0.6 +/- 0.5 mmol/h after its vehicle (P less than 0.05). Basal serum gastrin concentration increased significantly after progabide injection. Acid output during insulin-induced hypoglycemia was inhibited 59% by 30 mg/kg intravenous progabide. Progabide infusion also diminished or abolished circulating gastrin, somatostatin, and pancreatic polypeptide responses during insulin-induced hypoglycemia (P less than 0.05). Further studies were performed in dogs with a gastric fistula and a vagally denervated Heidenhain pouch to confirm that GABA-receptor stimulation affects acid secretion via peripheral pathways. Intravenous injection of baclofen (0.5 mg/kg), a GABAB-receptor agonist, increased acid secretion significantly from the gastric fistula and the Heidenhain pouch. These studies suggest that GABA may play a role in regulating gastric acid secretion and gastrointestinal and pancreatic endocrine function by both central and peripheral mechanisms.

Topics: Animals; Baclofen; Blood Glucose; Dogs; gamma-Aminobutyric Acid; Gastric Acid; Gastric Fistula; Gastrins; Gastrointestinal Hormones; Insulin; Male; Receptors, GABA-A; Vagus Nerve

The purpose of this study was to characterize the effects of aging on gastric acid secretion and on serum and antral concentrations of gastrin in rats. Young and old Fischer 344 rats were prepared with gastric fistulas. Twenty-four hours after surgery, graded doses of human synthetic gastrin-17 (SHG-17) (2, 5, 10, 20, and 40 micrograms/kg) were given intravenously in random order. Gastric secretions were collected for gastric acid measurement before and at 15-min intervals after each dose of gastrin. In a separate study, blood was collected and the stomachs were removed for antral gastrin extraction from fed young and old rats. Serum and antral gastrin was measured by radioimmunoassay. The basal and gastrin-stimulated acid secretions were significantly decreased in aged rats compared to the young rats. The basal acid output was 0.4 +/- 0.2 microeq/15 min in the aged rats and 1.5 +/- 0.5 microeq/15 min in the young. The maximal acid output stimulated by gastrin was 11.1 +/- 1.8 microeq/15 min in the aged rats and 24.2 +/- 2.8 microeq/15 min in the young. Both serum and antral concentrations of gastrin were significantly decreased in aged rats. Serum gastrin concentration was 114.8 +/- 7.4 pg/ml in the aged rats and 192.0 +/- 14.4 pg/ml in the young. Antral gastrin concentration was 3.9 +/- 0.5 micrograms/g tissue in the aged rats, which was significantly less than the concentration in the young (6.5 +/- 0.4 micrograms/g tissue). Antral gastrin content did not change with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Gastric Acid; Gastric Fistula; Gastrins; Hormones; Male; Pyloric Antrum; Rats; Rats, Inbred F344

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 mammalian counterpart to bombesin, gastrin-releasing peptide (GRP), is considered to stimulate gastric acid secretion by release of endogenous gastrin. The present study was carried out to examine if GRP has a stimulatory action on acid secretion in addition to that produced by released gastrin. In 4 gastric fistula (GF) and Heidenhain pouch (HP) cats, 160 pmol X kg-1 X h-1 i.v. GRP produced a GF and HP acid response that amounted to 22 and 13%, respectively, of the maximal acid response to pentagastrin, with no rise in serum gastrin concentration. GRP significantly increased the maximal acid response to pentagastrin in the GF but not in the HP. These results suggest that GRP stimulates acid secretion in cats also by an action not related to the release of gastrin. This action is greater in the presence of vagal innervation.

Topics: Animals; Cats; Gastric Acid; Gastric Fistula; Gastrin-Releasing Peptide; Gastrins; Pentagastrin; Peptides; Vagotomy

Postvagotomy hypergastrinemia may result from withdrawal of tonic vagal inhibitory mechanism(s) or from G-cell hyperplasia secondary to diminished acid secretion. Early development of hypergastrinemia, after vagotomy, would favor the first mechanism, whereas delayed development would favor the second. We sought to distinguish between these two mechanisms and to determine whether alterations in somatostatin release might mediate postvagotomy hypergastrinemia. We measured plasma concentrations of gastrin and somatostatinlike immunoreactivity basally and in response to meal (pH controlled at 5.5) and to insulin hypoglycemia before and after truncal vagotomy in 11 dogs. Basal and postprandial hypergastrinemia were established within 24 and 48 h after vagotomy, respectively. Basal and meal-stimulated plasma somatostatinlike immunoreactivity concentrations were unaltered by vagotomy, although insulin hypoglycemia-induced rises in plasma somatostatinlike immunoreactivity were abolished by vagotomy. Our data suggest that neither G-cell hyperplasia nor alterations in somatostatin release explain postvagotomy hypergastrinemia in the dog. The observations support the hypothesis that postvagotomy hypergastrinemia results from the withdrawal of a tonic vagal inhibitory mechanism of gastrin release that is independent of somatostatin. Whether the tonic vagal inhibition of gastrin is direct or indirect is unknown.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Gastric Acid; Gastric Fistula; Gastrins; Histamine; Hypoglycemia; Insulin; Postoperative Period; Somatostatin; Time Factors; Vagotomy

We investigated the effects of prostaglandins (PG) of E, F, and I series and their stable analogues on gastric acid secretion, serum gastrin level, and growth of gastroduodenal mucosa and pancreas in rats. Short-term administration (every 8 h for 48 h) of E and F series PGs and their stable analogues caused significant stimulation of DNA synthesis; prolonged PG treatment (every 8 h for 10 days) significantly increased weight and total DNA and RNA contents of the organs tested. PGs of E series were given in doses that inhibited gastric acid secretion about 50% and raised serum gastrin significantly; PGs of F series were injected in the same dose (1,000 micrograms/kg) as PGs of E series but did not affect acid secretion or serum gastrin. Short- or long-term treatment with PGI2 or its stable analogue (Hoe 892), injected in doses causing about 50% inhibition of acid secretion and significant increments in serum gastrin levels, failed to affect any of the growth-related parameters in the stomach, duodenum, or pancreas. We conclude that PGs of E and F (but not of I) series exhibit a marked stimulatory influence on growth of gastroduodenal mucosa and pancreas. These trophic effects appear to be unrelated to gastric secretion or serum gastrin release.

Topics: Animals; DNA; Dose-Response Relationship, Drug; Duodenum; Epoprostenol; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Intestinal Mucosa; Male; Organ Size; Pancreas; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains

Intravenously injected synthetic ovine corticotropin-releasing factor inhibited gastric secretion by reducing gastric secretory volume, acid concentration, and acid output, but elevated plasma gastrin levels in conscious 2-h pylorus-ligated rats. Corticotropin-releasing factor suppressed pentagastrin-stimulated gastric acid output at intravenous doses of 4-17 nmol X kg-1 X h-1 in urethane-anesthetized, gastric fistula rats and at 0.1-1-nmol X kg-1 X h-1 doses in conscious, gastric-fistula dogs. The inhibitory effect of corticotropin-releasing factor was dose-dependent, long-lasting, and reversible. The other newly characterized hypothalamic-hypophysiotropic peptide, growth hormone-releasing factor, hpGRF (1-40), infused at a dose of 18 nmol X kg-1 X h-1, did not modify gastric acid secretion stimulated by pentagastrin in rats. Gastric response to corticotropin-releasing factor in rats was altered neither by naloxone (5 mg/kg i.p.) or indomethacin (10 mg/kg i.p.) pretreatment, nor by hypophysectomy or adrenalectomy, but was partly reversed by vagotomy. These results demonstrate that corticotropin-releasing factor inhibits gastric acid secretion in both rats and dogs. The inhibitory effect of corticotropin-releasing factor on gastric secretion does not require the presence of the pituitary or the adrenal glands, or a functional prostaglandin biosynthetic pathway, and is not mediated through changes in gastrin secretion. It appears to be partially dependent on a degree of vagal tone as well as other mechanisms that await further elucidation.

Topics: Adrenalectomy; Animals; Corticotropin-Releasing Hormone; Dogs; Gastric Acid; Gastric Fistula; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Hypophysectomy; Male; Pentagastrin; Pylorus; Rats; Rats, Inbred Strains; Vagotomy

In conscious dogs with gastric and duodenal Thomas fistulas, we studied the effect of ethanol on plasma concentrations of gastrin. Ethanol was given either as an infusion into a peripheral vein (1.95 M, 200 ml/hr) or into the duodenum (0.95 M, 400 ml/hr) or as an intragastric bolus injection. The effect of the intragastric bolus injection of 200 ml of different concentrations (0.3 M, 1.7 M, 6.85 M) of ethanol was compared with that of equimolar solutions of urea and sucrose (0.3 M, 1.56 M), and with that of sodium taurocholate (0.06 M) and distilled water. The gastrin responses to an oral mixed-meat meal (35 g/kg) were also investigated. Intragastric bolus injection of isoosmolar (0.3 M) ethanol, but not of equimolar solutions of urea and sucrose or H2O, significantly (P less than 0.05) increased plasma gastrin levels above basal. Hyperosmolar solutions of ethanol, urea, and sucrose as well as hypoosmolar sodium taurocholate produced a pronounced increase of plasma gastrin concentrations above basal. The comparison of the mean 2-hr integrated plasma gastrin responses (IRG) showed that ethanol (6.85 M), urea (6.85 M), and sodium taurocholate (0.06 M) are at least as potent stimuli of release of gastrin as the test meal used. Intraduodenal and intravenous infusion of ethanol did not significantly alter mean plasma gastrin concentrations. We conclude that in the dog ethanol, but not urea and sucrose, given in a concentration (0.3 M) which is known not to disrupt the gastric mucosal barrier, increases plasma gastrin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Dogs; Duodenum; Ethanol; Food, Formulated; Gastric Fistula; Gastrins; Intestinal Fistula; Sucrose; Taurocholic Acid; Urea

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

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

The inhibition of gastrin 17-stimulated acid secretion by a partially purified cholecystokinin preparation (PcB) containing 1.2% cholecystokinin and 0.7% gastric inhibitory polypeptide immunoreactivity was compared with the inhibition produced by immunopurified cholecystokinin, cholecystokinin-depleted PcB, and gastric inhibitory polypeptide in 6 dogs with gastric fistulas. The dose-response curves for PcB and "pure" cholecystokinin were parallel and relative inhibitory potency of the pure peptide was 1.2. Dose-response curves of gastric inhibitory polypeptide and cholecystokinin-depleted PcB were similar, nonparallel to cholecystokinin dose response, and demonstrated potency significantly lower than that of PcB. When prepared without human albumin there were significantly higher losses of cholecystokinin-immunoreactivity by nonspecific adsorption from pure cholecystokinin solutions compared with PcB solutions. We conclude that inhibition of gastrin-stimulated acid secretion by partially pure cholecystokinin preparations can be explained by their cholecystokinin content and that previously reported differences in inhibitory potencies may be explained by nonspecific adsorption to glass from protein-free solutions.

Topics: Animals; Cholecystokinin; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Gastric Acid; Gastric Fistula; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Stimulation, Chemical

In this study we demonstrate that bombesin is a potent stimulant of canine gastrin and gastric acid secretion. Bombesin was shown to release almost fourfold more gastrin than a meal by a mechanism which is independent of vagal integrity. An exogenously administered cholinomimetic agent released only minimal amounts of gastrin after vagotomy and virtually none in the intact canine model. The combination of bombesin and bethanechol caused a significant increase in acid secretion compared with bombesin alone and was associated with a marked inhibition of gastrin release both before and after vagotomy. Gastric acid secretion in response to bombesin was not significantly altered by vagotomy. We interpret these data to reflect the sensitivity of bombesin-stimulated gastrin release to gastric luminal pH, although they also suggest the existence of a cholinergic inhibitory mechanism for gastrin release. The data provided by this study are consistent with the hypothesis that bombesin might function as a paracrine neuromodulator of gastrin release. in view of its presence in the nerves and mucosa of human stomach and its potent actions on gastrin release and gastric acid secretion, bombesin may play a role in gastric physiology.

Topics: Animals; Bethanechol Compounds; Bombesin; Dogs; Gastric Acid; Gastric Fistula; Gastrins; Meat; Peptides; Stimulation, Chemical; Vagotomy; Vagus Nerve

Concentrations of pancreatic polypeptide (PP) in peripheral blood were measured before, during, and after infusions of graded doses of synthetic human gastrin I (SHG-I), cholecystokinin 99% pure (CCK-99%), CCK octapeptide (CCK-OP), and pure natural porcine secretin in six dogs with gastric and duodenal fistulas. Studies were repeated after truncal vagotomy. Significant increases in concentrations of PP were found with 1 microgram . kg-1 . h-1 of SHG-I, 0.25 and 1.0 microgram . kg-1 . h-1 of CCK-99%, and 0.06 and 0.25 micrograms . kg-1 . h-1 of CCK-OP. Significant increases persisted after vagotomy, except at the lower dose of CCK-OP. Postvagotomy responses were significantly less than prevagotomy, except at the higher doses of CCK-99% and CCK-OP. Pure secretin did not change concentrations of PP in blood before or after vagotomy. The most potent stimulant for PP release on a molar basis was CCI-99%, followed by CCK-OP and SHG-I. The results suggest that cholinergic and humoral agents of the gastrin-cholecystokinin family interact in the normal physiological response of PP to food and that, in dogs, CCK-like peptides are more potent than gastrin.

Topics: Animals; Cholecystokinin; Dogs; Dose-Response Relationship, Drug; Gastric Fistula; Gastrins; Pancreas; Pancreatic Polypeptide; Secretin; Vagus Nerve

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; Dogs; Dose-Response Relationship, Drug; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Pepsin A; Pyloric Antrum

Topics: Animals; Betazole; Dogs; Ethanol; Gastric Emptying; Gastric Fistula; Gastrins; Insulin; Nerve Tissue; Pentagastrin; Vagotomy

Three synthetic preparations of big gastrin (G-34), little gastrin (G-17) and minigastrin (G-14) have been compared with regard to gastric acid stimulatory potency, rate of disappearance and the relation between acid secretion and the change in serum immunoreactive gastrin in gastric fistula and Heidenhain pouch dogs. Equimolar graded doses (12.5 to 200 pmol/kg-hr) of G-14, G-17 and G-34 produced similar rates of acid secretion with equal ED50 for all three gastrin peptides. Equimolar doses of G-14 and G-17 also resulted in similar increments in serum immunoreactive gastrin, but those of G-34 caused approximately two to three times greater increments in serum gastrin than did G-14 or G-17. The disappearance half-times determined by measuring serum gastrin at short intervals after discontinuation of equimolar dose (1000 pmol/kg-hr) infusions of each gastrin peptide were 1.75, 4.85 and 11.53 min for G-14, G-17 and G-34, respectively. The calculated space of distribution was similar for all three gastrin preparations and ranged from 20-30% body weight. These results indicate that the three major gastrin components differ in half-times and in relating secretory potency, in that relatively higher molar concentrations of G-34 than G-14 or G-17 were required to produce equal rates of acid secretion.

Topics: Animals; Antibodies; Dogs; Gastric Acid; Gastric Fistula; Gastrins; Half-Life; Metabolic Clearance Rate; Radioimmunoassay; Secretory Rate

In dogs provided with Heidenhain pouch and gastric fistula, we studied the effect of near-total excision of the fundic mucosa of the main stomach on acid secretion and gastrin release. Fundic mucosal excision abolished the mean response of the gastric fistula and reduced its maximal response to pentagastrin and to histamine by 85%. The basal Heidenhain pouch acid output increased ninefold, and fasting levels of serum gastrin increased from 36 +/- 3 pg/ml before the 248 +/- 47 pg/ml after fundic mucosa excision. The peak gastrin response to meal rose from 168 +/- 12 before to 392 +/- 49 pg/ml after. This increase could not have been due to changes in pH during the meal as meal pH was held constant at 5.5 by the method of intragastric titration in both pre- and postexcision studies. Following fundic mucosal excision, the acid response of the Heidenhain pouch to meal and to both submaximal and maximal doses of pentagastrin and histamine increased markedly. The maximal response to the meal increased from 41 +/- 9 before to 167 +/- 43 after, expressed as percent of the preexcision maximal histamine output. The corresponding changes in the maximal responses to pentagastrin respectively before to 124 +/ 26 and 230 +/- 31 after, again expressed as percent of the preexcision maximal histamine output. These observations suggest that fundic mucosal excision removes an inhibitory mechanism of both acid secretion and gastrin release.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Female; Gastric Acid; Gastric Fistula; Gastric Fundus; Gastric Mucosa; Gastrins; Histamine; Hydrogen-Ion Concentration; Pentagastrin; Vagotomy; Vagus Nerve

The effect of intravenous infusion of L-amino acids (FreAmine II) on gastric secretion and on circulating levels of gastrin was studied in five gastric fistula dogs and three dogs with portacaval transposition. Significant increases in gastric acid secretion were found after infusions which delivered 2.0, 4.0, and 8.0 gm/hr of L-amino acids in five gastric fistula dogs. After portacaval transposition, administration of amino acid solutions via the hindleg (through the liver) resulted in a great fall in the acid secretory response. Gastrin levels were significantly elevated after 8.0 gm/hr of amino acids. After 2.0 and 4.0 gm/hr, there was a slight but insignificant increase in serum gastrin levels. Gastrin levels were unchanged after infusion of 8.0 gm/hr of L-amino acids through the liver. We conclude that L-amino acids given intravenously stimulate gastric acid secretion in a dose-dependent manner by a mechanism which does not involve gastrin. At the highest dosage of amino acids, some gastrin was released which might have stimulated acid output further.

Topics: Amino Acids; Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Infusions, Parenteral; Portacaval Shunt, Surgical; Portal Vein; Solutions; Vena Cava, Inferior

Topics: Animals; Atropine; Cimetidine; Dogs; Female; Gastric Fistula; Gastric Juice; Gastrins; Guanidines; Histamine; Injections, Intramuscular; Male; Stimulation, Chemical; Tetragastrin

Responses of serum gastrin and gastric acid output levels were studied in four dogs before and after a bilioenteric by-pass. Serum gastrin levels during bombesin infusion were measured in eight patients submitted to Roux-en-Y hepatocholangiojejunostomy. No change was observed in acid secretion from the main stomach or from the Heidenhain pouch in dogs following biliojejunostomy. The peak acid output, however, occurred significantly earlier after diversion of bile from the duodenum. Serum gastrin levels decreased significantly in dogs after bilioenteric by-pass and in the operated patients compared with normal subjects. The possible role played by bile in the release of duodenal gastrin is hypothesized.

Topics: Adult; Animals; Bile; Bombesin; Common Bile Duct; Dogs; Female; Gastric Fistula; Gastric Juice; Gastrins; Humans; Jejunum; Liver; Male; Middle Aged; Secretory Rate

The secretory potency and disappearance rates of pure synthetic human non-sulphated minigastrin (HG-14-I) and pure natural human non-sulphated heptadecapeptide (HG-17-I) were compared in five dogs with gastric fistulas and Heidenhain pouches. Intravenous infusion of equimolar doses of the two gastrins produced equimolar increases over basal of serum immunoreactive gastrin and no statistically significant differences in acid output. Also HG-14-I and HG-17-I did not differ significantly in half-times for disappearance, clearance rates, calculated volumes of distribution, or mean plateau serum levels.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Gastric Fistula; Gastric Juice; Gastrins; Hormones; Metabolic Clearance Rate; Secretory Rate

Bombesin and a synthetic bombesin nonapeptide were studied by intravenous infusion at a dose of 0.5 microgram.kg-1.h-1 for 4 h in 7 dogs with esophagostomy and gastric fistula. In 3 of the dogs who had highly selective (fundic) vagotomy, mean integrated gastrin output over 4 h was double that in the 4 dogs with vagi intact during both nonapeptide (1,554 vs. 700 pg.ml-1.4 h-1) and bombesin infusion (2,442 vs. 1,440 pg.ml-1.4 h-1). Peak concentrations of serum gastrin reached during bombesin (490 +/- 100 vs. 320 +/- 90) were higher than those during nonapeptide infusion (270 +/- 40 vs. 160 +/- 28 pg/ml) in the vagotomized and intact dogs, respectively. The difference between vagotomized and vagally intact dogs suggests that the fundic vagotomy removed an inhibitor of gastrin release from the innervated antrum. Despite these differences in gastrin release, gastric acid output with the two peptides was the same (49--52 mEq/4 h) whether the fundus was denervated or innervated. This suggests that bombesin may stimulate gastric acid secretion by the release of an additional secretagogue which is not measured by the gastrin assay. Neither of the two inhibitors of gastrin release--antral acidification to pH 1.4 or less or atropine (100 microgram/kg)-- inhibited gastrin release by bombesin, even though the atropine reduced acid output by 80%. Bombesin is a potent gastric stimulus whose action is only partly explained by the measured gastrin release.

Topics: Animals; Atropine; Bombesin; Dogs; Esophagus; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Infusions, Parenteral; Pepsin A; Peptides; Pyloric Antrum; Secretory Rate; Vagotomy

Topics: Animals; Atropine; Bethanechol Compounds; Dogs; Eating; Female; Gastric Fistula; Gastric Juice; Gastrins; Hexamethonium Compounds; Histamine; Male; Prostaglandins E; Quaternary Ammonium Compounds; Radioimmunoassay; Secretin; Tetragastrin

Gastric H+ and pepsin studies before and at intervals for 4o months after fundic vagotomy (HSV) in 3 fistula dogs were done with the vagal stimulant 2-deoxyglucose (2-DG), and blocked the secretory response to 2-DG, but secretion began to recover by 5-6 months, and from 16 months on stabilized at 60% H+ and 13-17% pepsin (preoperative = 100%). After HSV the stomach showed hypersensitivity to urecholine with a lower threshold and lower Km, but unchanged Vm, while with histamine the curves were shifted to the right, with Vm unchanged and Km increased. With pentagastrin there was also a small decrease in Vm. Pepsin responses to urecholine recovered and exceeded control by 16 months, but remained relatively unresponsive to histamine or pentagastrin. A cholinergic background provided by urecholine at subthreshold doses (less than 10 mug/kg-hr) restored both pentagastrin and histamine responses to prevagotomy levels. Gastrin release from the innervated antrum by 2-DG was several times greater than in controls and was atropine sensitive. The results indicate that denervation of the secretory mucosa, especially of the peptic cells, is never more than partially reversed even after 3 years. Even though the response to vagal stimulation is partial, the mucosa remains capable of normal response, ie, there is no atrophy, and therefore, the vagus is not directly trophic to the gastric fundus. Moreover, vagotomy was followed by some hypersensitivity to urecholine, indicating changes in cholinergic receptors like those seen in denervated muscle cells.

Topics: Acetylcholine; Animals; Bethanechol Compounds; Deoxyglucose; Dogs; Dose-Response Relationship, Drug; Electrolytes; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Kinetics; Models, Biological; Pentagastrin; Pepsin A; Receptors, Cholinergic; Vagotomy

The effect of gastrin on DNA synthesis and mitotic activity in the mucosa of the upper-gastrointestinal tract was explored in unanesthetized rats with a gastric fistula. Animals were killed at 4-hr intervals, after starting a 3-hr intravenous infusion with the lowest dose of gastrin provoking a maximal acid output. Tritiated thymidine was injected 1 hr before killing. Autoradiography was used, and labeling and mitotic indices were estimated in the fundic, antral, duodenal, and jejunal mucosa. The proliferative activity in the fundic, duodenal, and jejunal glands was significantly increased 16 hr after the administration of gastrin. In the antral glands, however, a significant decrease in both labeling and mitotic indices was observed. Rhythmic variations in proliferative activity were observed in the antral, duodenal, and jejunal mucosa in control animals. They were different from those in the gastrin-treated animals. Our data confirm the trophic action of gastrin in the fundic, duodenal, and jejunal mucosa. They also indicate an inhibitory effect of this hormone on cell proliferation in the antral mucosa.

Topics: Animals; Autoradiography; Cell Division; Circadian Rhythm; Digestive System; DNA; Duodenum; Gastric Fistula; Gastrins; Intestinal Mucosa; Jejunum; Male; Mitotic Index; Pyloric Antrum; Rats; Thymidine

The effect of graded doses of synthetic human gastrin and pentagastrin on gastric secretion from the innervated and denervated stomach was measured in dogs. The circulating levels of gastrin during the infusion of this hormone were also estimated. The increase in gastrinemia for a fixed dose of exogenous gastrin differed from dog to dog. The dose for half-maximal response to gastrin was negatively correlated with the observed increase in serum gastrin. This suggests that the disposal rate of gastrin influences the calculated sensitivity of the parietal cells to this hormone. In the gastric fistula and in the pouch, maximal acid responses for gastrin and pentagastrin were linearly correlated, but doses for half maximal responses were not. This indicates that step-dose infusion of pentagastrin may be used to estimate the maximal acid response to gastrin, but it is not proven that such a test is useful to estimate the sensitivity of the parietal cells to gastrin in individual dogs.

Topics: Animals; Dogs; Female; Gastric Fistula; Gastric Juice; Gastrins; Male; Pentagastrin; Stimulation, Chemical

Acid secretion in Pavlov pouches in dogs is known to increase after antrectomy in response to histamine and gastrin. Dogs with gastric fistulae were tested with histamine and tetragastrin as a control study. The vagal nerve fibers to the antrum were divided and the dogs underwent repeat testing. Finally an antrectomy was performed and final dose-response data were collected. After antrectomy there was an increased acid response to histamine and tetragastrin. We postulate that the vagal fibers innervating the antrum are probably not a factor in this increase. Furthermore, we believe that the increased acid secretion after antrectomy observed in the dog and the decrease known to occur in the human being is a species difference and is not related to the pouch method of study used in earlier studies of the antrectomized dog.

Topics: Animals; Denervation; Dogs; Dose-Response Relationship, Drug; Duodenum; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Humans; Pyloric Antrum; Species Specificity; Stimulation, Chemical; Vagotomy; Vagus Nerve

Topics: Amino Acids; Animals; Denervation; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Perfusion; Pyloric Antrum; Pylorus; Stereoisomerism; Stomach

Changes in serum gastrin in response to feeding a meal of beef liver (15 g kg(-1)) were studied in 5 gastric fistula dogs with and without administration of atropine sulfate (0.2 mg kg(-1) intravenously). The studies were repeated after a truncal vagotomy that abolished acid secretion in response to 2-deoxyglucose. Before vagotomy atropine had little effect on the gastrin response to a meal. After vagotomy the gastrin response to feeding was greatly enhanced, but now atropine depressed the gastrin response at all times after the meal. It is concluded that vagotomy enhances the serum gastrin response to feeding and that atropine counteracts this enhancement.

Topics: Animals; Atropine; Deoxyglucose; Depression, Chemical; Dogs; Fasting; Food; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Vagotomy

Heidenhain pouches were established in four mongrel dogs. Acid secretory values were studied in response to a meal, both after operation and six to eight months later. Large increases in the acid responses of the Heidenhain pouch to a meal were noted over a period of time. Mechanisms accountable for this acid increase were studied, including serum gastrin response, pepsin activity, and morphologic changes in the pouch. Regeneration or reinnervation of vagal fibers may occur at a subthreshold level but is not well documented. The necessity of repeated control studies in long-term evaluation using the Heidenhain pouch is emphasized.

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Meat; Pepsin A; Stomach

Topics: Animals; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Intestinal Absorption; Liver Extracts; Pentagastrin; Perfusion; Radioimmunoassay; Vagotomy

Instillation of liver extract into antral pouches produced an increase in the serum concentrations of both little (G-17) and big (G-34) gastrins. The molar fraction of G-17 plus G-34 represented by G-17 was about 0.9 in antral mucosa and about 0.3 in serum 3 hr after initiating release with liver extract. The predominance of G-34 in serum can be accounted for only in part by its slower rate of removal from the blood so other factors probably also contribute. Although G-17 contributed only about 30% of the total molar concentration of gastrins in serum, it accounted for about 70% of the acid stimulatory activity because on a molar basis it is about five times more bioactive than G-34.

Topics: Animals; Antibodies; Biopsy; Chromatography, Gel; Denervation; Dogs; Fasting; Gastric Fistula; Gastric Mucosa; Gastrins; Liver Extracts; Molecular Conformation; Stomach; Time Factors

Acid secretory and serum gastrin responses to 2-deoxy-D-glucose and insulin were compared in gastric fistula dogs before and after partial vagotomy and pyloroplasty or partial vagotomy and antrectomy. The acid response and serum gastrin curve were basically unaltered by partial vagotomy and pyloroplasty. Based on the data presented, the acid response to insulin hypoglycemia appears to be more dependent on the vagal release of antral gastrin than on direct vagal stimulation of the parietal cell. However, acid response to insulin was profoundly suppressed to only 4 per cent of control levels after partial vagotomy and antrectomy. Although acid response to 2-deoxy-D-glucose was also profoundly depressed to 33 per cent of control levels after partial vagotomy and antrectomy, it was seven times greater than that seen with insulin. Serum gastrin response was abolished after antrectomy to either insulin or 2-deoxy-D-glucose. Finally, the question to which we originally addressed ourselves appears to have been answered and, in terms of response to vagal stimulation, antrectomy appears to compensate for incomplete vagal denervation and may lead to aberrations and misinterpretations, raising serious questions as to the validity of the Hollander test in patients who have undergone distal gastric resection.

Topics: Animals; Deoxyglucose; Dogs; Drainage; Evaluation Studies as Topic; Gastric Fistula; Gastrins; Insulin; Pyloric Antrum; Stimulation, Chemical; Vagotomy; Vagus Nerve

Topics: Animals; Blood Specimen Collection; Dogs; Ethylamines; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Liver Extracts; Perfusion; Pyloric Antrum; Pyrazoles; Radioimmunoassay; Specimen Handling; 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; Bicarbonates; Cold Temperature; Dogs; Gastric Fistula; Gastrins; Hydrochloric Acid; Hypoglycemia; Injections, Intravenous; Insulin; Pyloric Antrum; Stimulation, Chemical; Vagus Nerve

1 The intravenous infusion of bombesin produced in intact dogs and, more strikingly in dogs provided with gastric fistulae a sharp increase in plasma levels of immunoreactive gastrin and at the same time a stimulation of gastric acid secretion. Gastrin response was correlated with the dose of bombesin from approximately 0.1 mug kg(-1) h(-1) (threshold) to 1 mug kg(-1) h(-1) (maximum gastrin release).2 Atropine and metiamide reduced or inhibited gastric acid secretion stimulated by bombesin, but did not affect the rise in gastrin levels.3 Acidification of the whole stomach or of a perfused antral pouch caused a reduced or delayed response to bombesin. However, the inhibitory effect of acidification could be surmounted by prolonging the duration of bombesin infusion.4 Antrectomy greatly reduced the rise in gastrin levels and the increase in acid gastric secretion produced by bombesin, but left unaffected the gastric secretagogue effect of pentagastrin.5 It is concluded that bombesin is a potent releaser of gastrin from the antral mucosa.6 The possible influence of the renal effects evoked by bombesin in the dog on the gastrin response to the polypeptide is discussed.

Topics: Animals; Anura; Atropine; Dogs; Gastric Fistula; Gastrins; In Vitro Techniques; Iodine Radioisotopes; Peptides; Pyloric Antrum; Radioimmunoassay; Skin; Swine; Time Factors; Tissue Extracts

Topics: Animals; Blood Glucose; Chronic Disease; Depression, Chemical; Dogs; Dose-Response Relationship, Drug; Gastric Fistula; Gastric Juice; Gastrins; Insulin; Stimulation, Chemical; Time Factors

Topics: Animals; Chymotrypsinogen; Depression, Chemical; Dogs; Duodenum; Fasting; Freeze Drying; Gastric Fistula; Gastric Juice; Gastrins; Intestinal Fistula; Pancreatic Extracts; Pancreatic Juice; Pepsin A; Secretory Rate; Stimulation, Chemical; Stomach; Trypsin; Trypsinogen

Topics: Acetylcholine; Animals; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Meat; Stimulation, Chemical; Stomach; Therapeutic Irrigation; Vagotomy; Vagus Nerve

Topics: Animals; Colon; Denervation; Dogs; Ethanol; Female; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Hyaluronoglucosaminidase; Male; Methods; Peptic Ulcer; Stomach; Transplantation, Autologous

Topics: Adrenergic beta-Antagonists; Amino Alcohols; Animals; Butoxamine; Dogs; Female; Gastric Fistula; Gastric Juice; Gastrins; Glucagon; Histamine H1 Antagonists; Pentagastrin; Phenoxybenzamine; Potassium Chloride; Propranolol; Time Factors

Topics: Animals; Blood Glucose; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Glucose; Histamine; Pentagastrin; Potassium; Pyloric Antrum; Secretory Rate; Stimulation, Chemical; Vagus Nerve

Topics: Animals; Cell Count; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Male; Pyloric Antrum; Rats

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Humans; Iodine Isotopes; Kidney; Metabolic Clearance Rate; Urine

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Half-Life; Injections, Intravenous; Metabolic Clearance Rate; Regression Analysis; Secretin; Stimulation, Chemical

Topics: Animals; Carbon Isotopes; Carboxy-Lyases; Gastrectomy; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Glycyrrhiza; Histidine; Injections, Intraperitoneal; Male; Plant Extracts; Plants, Medicinal; Radioimmunoassay; Rats

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Glucagon; Secretin; Stomach; Swine

Topics: Animals; Dogs; Esophagus; Feeding Behavior; Gastrectomy; Gastric Fistula; Gastric Juice; Gastrins; Gastrointestinal Hormones; Pentagastrin; Pepsin A; Peptides; Stomach; Time Factors

1. In conscious rats provided with Pavlov or Heidenhain pouches the acid and pepsin responses to vagal stimulation, or infusions of gastrin, histamine, methacholine, and to various combinations of these stimulants have been established. The concomitant mobilization and increased formation of gastric mucosal histamine have also been examined.2. Histamine evoked graded acid responses in the Pavlov and Heidenhain pouches. The innervated pouch was more sensitive to histamine than the denervated. Stimulation of pepsin secretion was apparent only in the Heidenhain pouch.3. The acid response to vagal stimulation evoked by 2-deoxy-D-glucose was facilitated by infusion of histamine, but not that of pepsin, the secretion of which was depressed.4. Acid secretion in response to graded infusion of methacholine was enhanced by background infusions of histamine in subthreshold, sub-maximal and maximal dosages.5. The acid response to vagal stimulation was enhanced by a background infusion of gastrin, but not that of pepsin, the secretion of which was depressed.6. A background infusion of a large dose of histamine depressed the maximal acid response to gastrin in both types of pouches.7. Administration of histamine restrained the accelerating effect of gastrin on histidine decarboxylase activity, probably by a feed-back coupling.8. The increase in gastric mucosal histamine, as reflected in its urinary excretion, in response to gastrin infusion was enhanced by vagal stimulation.9. The amounts of histamine that can be mobilized and newly formed in the gastric mucosa have been evaluated and found to be fully adequate for efficient stimulation of the parietal cell.

Topics: Animals; Carboxy-Lyases; Feedback; Female; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Glucose; Histamine; Methacholine Compounds; Pepsin A; Rats; Secretory Rate; Stimulation, Chemical; Stomach; Vagus Nerve

Topics: Acetylcholine; Analysis of Variance; Animals; Blood Glucose; Dogs; Duodenum; Eating; Gastric Fistula; Gastric Juice; Gastrins; Hypoglycemia; Immunoassay; Insulin; Muscle Denervation; Pepsin A; Pyloric Antrum; Stimulation, Chemical; Vagus Nerve

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Hypoglycemia; Insulin; Meat; Stomach; Vagus Nerve

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Hypoglycemia; Insulin; Meat; Stomach; Vagotomy

Topics: Animals; Bethanechol Compounds; Cats; Dose-Response Relationship, Drug; Drug Synergism; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Injections, Intravenous; Pentagastrin; Stimulation, Chemical

Topics: Animals; Cats; Duodenum; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Injections, Intravenous; Secretin; Species Specificity

Topics: Animals; Bile; Cats; Ceruletide; Cholecystokinin; Drug Synergism; Duodenal Ulcer; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Gastrointestinal Hormones; Infusions, Parenteral; Pancreatic Juice; Peptic Ulcer; Peptides

Topics: Animals; Atropine; Conditioning, Classical; Dogs; Eating; Fasting; Feeding Behavior; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Radioimmunoassay; Stimulation, Chemical; Time Factors

Topics: Animals; Dogs; Eating; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Pentagastrin; Stimulation, Chemical; Vagotomy; Vagus Nerve

Topics: Acetylcholine; Animals; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Insulin; Meat; Pepsin A; Peptides; Pylorus; Secretory Rate; Stimulation, Chemical; Stomach; Vagotomy

Topics: Animals; Cats; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Peptides; Stomach; Vagotomy; Vagus Nerve

Topics: Animals; Cats; Consciousness; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine; Humans; Secretory Rate; Stimulation, Chemical; Vagotomy; Vagus Nerve

Topics: Aminopyrine; Animals; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Glucagon; Hydrogen-Ion Concentration; Infusions, Parenteral; Secretory Rate

Topics: Animals; Aspartic Acid; Binding Sites; Cats; Cholecystokinin; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Peptides; Stimulation, Chemical; Stomach

Topics: Animals; Dogs; Duodenum; Gastric Fistula; Gastrins; Hydrochloric Acid; Kinetics

Topics: Animals; Bethanechol Compounds; Dogs; Duodenum; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Secretin; Secretory Rate; Stimulation, Chemical; Vagotomy; Vagus Nerve

Topics: Animals; Autonomic Nervous System; Denervation; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Gastrointestinal Hormones; Glycosaminoglycans; Injections, Intravenous; Intestinal Fistula; Intestine, Small; Jejunum; Oils; Vagus Nerve

Topics: Animals; Cholecystokinin; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Intubation, Gastrointestinal; Peptides; Stomach; Sulfates; Vagus Nerve

Topics: Animals; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Liver; Secretory Rate; Stimulation, Chemical; Stomach; Vagotomy; Vagus Nerve

Topics: Animals; Carbachol; Carboxy-Lyases; Denervation; Fasting; Gastric Fistula; Gastric Juice; Gastrins; Histidine; Hydrogen-Ion Concentration; Insulin; Male; Perfusion; Rats; Stomach; Vagotomy; Vagus Nerve

Topics: Acetylcholine; Animals; Dogs; Food; Gastric Fistula; Gastric Juice; Gastrins; Perfusion; Secretory Rate; Stomach; Time Factors; Vagus Nerve

Topics: Animals; Bethanechol Compounds; Cholecystokinin; Dogs; Gastric Fistula; Gastrins; Gastrointestinal Hormones; Peptides; Proteins; Saliva; Salivary Gland Fistula; Salivation; Secretin; Secretory Rate

Topics: Animals; Chlorides; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Hematocrit; Histamine; Homeostasis; Hydrogen; Kinetics; Pepsin A; Potassium; Potassium Chloride; Sodium; Stimulation, Chemical; Stomach; Time Factors; Water

Topics: Animals; Autoanalysis; Chlorides; Cholecystokinin; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Methacholine Compounds; Pepsin A; Peptides; Potassium; Pylorus; Stimulation, Chemical

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

1. The effects of the vagus nerve and of antral gastrin on the rate of histamine formation (histamine forming capacity, HFC, i.e. histidine decarboxylase activity) in the parietal cell region of the gastric mucosa has been investigated in the following stomach preparations: gastric fistula, denervated Heidenhain pouch, antral resection with gastrojejunostomy, gastrojejunostomy with exclusion of the duodenum and in the intact stomach. The determinations of mucosal HFC were made on fasting rats and on re-fed animals when the effect of feeding was studied.2. In fasting rats with a gastrojejunostomy and the antrum intact the mucosal HFC of the innervated stomach was about 4 times higher than in the corresponding preparation with the antrum resected. In the innervated main stomach the mucosal HFC was about twice as high as in the denervated pouch, indicating that the vagus and endogenous antral gastrin each contribute to maintaining mucosal HFC in the fasting state.3. Acidifying the stomach caused a substantial lowering of the mucosal HFC presumably by inhibiting antral gastrin release, whereas acid in the stomach did not interfere with the elevation of mucosal HFC evoked by injection of gastrin.4. Injection of gastrin elevated mucosal HFC in the innervated main stomach and in the denervated pouch to approximately equal levels. With the dose of gastrin employed there was about a fourfold increase in the HFC of the pouch mucosa.5. In antrectomized rats enhanced vagal influence, evoked by insulin injection or by feeding, raised the mucosal HFC. In rats with the antrum intact and the stomach acidified, insulin injection produced an increased HFC. Thus, a vagal effect on mucosal HFC exists independent of participation of antral gastrin.6. The stable choline esters carbachol and methacholine act directly on the parietal cell without involving mucosal HFC. The vagus nerve and gastrin, however, are assumed to provide secretory stimulation by means of accelerated histamine formation.7. The interrelation between increased histamine formation and hydrochloric acid secretion is discussed.

Topics: Animals; Carbachol; Denervation; Fasting; Female; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Gastroenterostomy; Histamine; Insulin; Male; Methacholine Compounds; Rats; Stomach; Vagus Nerve

Topics: Animals; Dogs; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine

Topics: Animals; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Hyperplasia; Male; Rats; Secretory Rate

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Hepatic Veins; Histamine; Inulin; Liver; Portal Vein; Stomach; Vena Cava, Inferior

Topics: Animals; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine; Histamine Release; Pepsin A; Rats

Topics: Acetylcholine; Acute Disease; Amides; Amino Acids; Animals; Bethanechol Compounds; Blood Pressure; Chronic Disease; Dogs; Drug Synergism; Gastric Fistula; Gastric Juice; Gastrins; Gastrointestinal Motility; Guinea Pigs; Histamine; Ileum; Male; Methacholine Compounds; Pepsin A; Peptides; Perfusion; Pylorus; Rats; Stomach; Tachyphylaxis

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

Topics: Animals; Dogs; Duodenum; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Hydrochloric Acid; Injections, Intravenous; Secretin

Topics: Animals; Autoradiography; Bethanechol Compounds; Biopsy; Dogs; Food; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastric Mucins; Gastric Mucosa; Gastrins; Histamine; Histocytochemistry; Injections, Intravenous; Injections, Subcutaneous; Stomach; Sulfur Isotopes

Topics: Animals; Cats; Dogs; Duodenal Ulcer; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Stomach; Tissue Extracts

Topics: Animals; Colon; Denervation; Dogs; Gastric Fistula; Gastric Mucosa; Gastrins; Hexoses; Histamine; Peptides; Phenylacetates; Pylorus; Pyridines; Stomach; Sulfhydryl Compounds

Topics: Animals; Dogs; Gastric Fistula; Gastric Mucosa; Gastrins; Hexoses; Histamine; Intestines; Pancreatic Ducts; Phenylacetates; Pyridines; Stomach; Sulfhydryl Compounds

Topics: Animals; Depression, Chemical; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Hexoses; Histamine; Male; Manometry; Rats; Secretory Rate; Stimulation, Chemical; Stomach

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

Topics: Animals; Gastric Fistula; Gastric Juice; Gastrins; Male; Povidone; Rats; Stomach

Topics: Animals; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Pepsin A; Secretory Rate; Vagotomy; Vagus Nerve

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Pepsin A; Secretory Rate; Stomach

Topics: Animals; Buffers; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Hydrogen-Ion Concentration; Neostigmine; Peptides; Perfusion; Stimulation, Chemical; Stomach

Topics: Animals; Dogs; Duodenum; Fats; Gastric Fistula; Gastrins; Gastrointestinal Motility; Jejunum; Stomach

Topics: Animals; Gastric Fistula; Gastric Juice; Gastrins; Rats; Secretory Rate; Stomach

Topics: Animals; Cats; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Injections, Intravenous; Injections, Subcutaneous; Peptides; Secretory Rate; Stomach; Vagotomy

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastric Mucosa; Gastrins; 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 Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Heparin; Pharmacology; Research

Topics: Animals; Bodily Secretions; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Pepsin A; Pharmacology; Research

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Pylorus

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

Topics: Animals; Atropine; Cats; Gastric Fistula; Gastric Juice; Gastrins; Reserpine; Stomach; Sympathectomy; Vagotomy

Topics: Animals; Dogs; Duodenum; Gastric Acid; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Intestinal Fistula; Physiology; Research; Secretin; Vagus Nerve

Topics: Cats; Gastric Acid; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Methacholine Compounds; Pharmacology; Physiology; Research; Reserpine; Vagotomy; Vagus Nerve

Topics: Animals; Dogs; Gastric Acidity Determination; Gastric Fistula; Gastric Juice; Gastrins; Histamine; Parasympathomimetics; Pepsin A; Pharmacology; Research; Vagotomy; Vagus Nerve

Topics: Animals; Gastric Fistula; Gastrins; Histamine; Injections; Rats

Topics: Animals; Dogs; Gastric Fistula; Gastrins; Histamine; Hydrochloric Acid; Pepsin A; Pharmacology; Physiology; Research; Vagus Nerve

Topics: Animals; Cats; Gastric Fistula; Gastric Juice; Gastrins; Gastrointestinal Hormones; Histamine; Infusions, Intravenous; Stomach