Maleic acid and succinic acid in fermented alcoholic beverages are the stimulants of gastric acid secretion.

Alcoholic beverages produced by fermentation (e.g., beer and wine) are powerful stimulants of gastric acid output and gastrin release in humans. The aim of this study was to separate and specify the gastric acid stimulatory ingredients in alcoholic beverages produced by fermentation. Yeast-fermented glucose was used as a simple model of fermented alcoholic beverages; it was stepwise separated by different methods of liquid chromatography, and each separated solution was tested in human volunteers for its stimulatory action on gastric acid output and gastrin release. Five substances were detected by high-performance liquid chromatography and were analyzed by mass spectrometry and 1H-13C nuclear magnetic resonance spectroscopy. At the end of the separation process of the five identified substances, only the two dicarboxylic acids, maleic acid and succinic acid, had a significant (P < 0.05) stimulatory action on gastric acid output (76% and 70% of fermented glucose, respectively), but not on gastrin release. When given together, they increased gastric acid output by 100% of fermented glucose and by 95% of maximal acid output. We therefore conclude that maleic acid and succinic acid are the powerful stimulants of gastric acid output in fermented glucose and alcoholic beverages produced by fermentation, and that gastrin is not their mediator of action.

Comparison of two dose-response techniques to study the pancreatic secretory response to intraduodenal tryptophan in the absence and presence of the M1-receptor antagonist telenzepine.

To answer the questions if the type of continuous dose-response technique influences the pancreatic secretory response to intraduodenal tryptophan and if the M1-receptor antagonist telenzepine influences the intestinal absorption of tryptophan, we determined, in 12 conscious dogs with chronic gastric and duodenal fistulas, pancreatic bicarbonate and protein secretion and tryptophan plasma concentrations following intraduodenal tryptophan perfusion using two dose-response techniques. With an ascending continuous dose-response technique (aDRT), tryptophan was perfused in loads ranging from 0.12 to 10.0 mmol h-1, starting with the lowest load and tripling it every 45 min. With the descending continuous dose-response technique (dDRT), the order of tryptophan loads was reversed, with the highest load being given first. All studies were done on a fixed background of intravenous secretin (20.5 pmol kg-1 h-1) and repeated in the presence of the anticholinergic M1-receptor antagonist telenzepine (243 nmol kg-1 h-1). The bicarbonate and protein response as well as tryptophan plasma concentrations to the same loads of tryptophan did not differ significantly between the two techniques. Using both techniques, telenzepine significantly (p < 0.05) inhibited the overall pancreatic protein response by 65% (dDRT) to 81% (aDRT). The overall bicarbonate response was only numerically, and not statistically significantly, inhibited by telezepine. Tryptophan plasma concentrations after duodenal perfusion with tryptophan were neither influenced by the order of tryptophan loads nor altered by telenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic secretory response to intrajejunal tryptophan: studies in dogs with an autotransplanted entire jejunoileum.

In two sets of dogs with gastric, duodenal, and jejunal fistulas, we studied the effect of atropine (14 nmol/ kg/h) on the pancreatic secretory response to intrajejunal tryptophan (0.12-10.0 mmol/h; given against a secretin background) before (n = 7) and after extrinsic denervation of the jejunoileum (orthotopical autotransplantation; n = 6). Plasma levels of cholecystokinin were determined by radioimmunoassay. The incremental bicarbonate response to tryptophan was not significantly different between the two sets of dogs. Atropine had no effect on the incremental bicarbonate response to tryptophan. In both sets of dogs, intrajejunal tryptophan caused a dose-dependent increase in pancreatic protein output, which was reduced by atropine. The tryptophan-stimulated levels of plasma cholecystokinin were not significantly altered by denervation and or atropine. We conclude that in dogs (1) intrajejunal tryptophan stimulates pancreatic bicarbonate and protein secretion via release of hormones, (2) extrinsic denervation of the jejunoileum does not significantly alter the incremental bicarbonate and protein responses to intrajejunal tryptophan, (3) the cholinergic intrinsic nerves of the jejunoileum and the hormone cholecystokinin are probably involved in control of the pancreatic protein response to tryptophan, and (4) the release of cholecystokinin by intrajejunal tryptophan does not depend on the extrinsic and intrinsic cholinergic nerves of the jejunoileum.

Comparison of the effects of the M1-receptor antagonist telenzepine and the CCK-receptor antagonist loxiglumide on the pancreatic secretory response to intraduodenal tryptophan in dogs.

In six conscious dogs with chronic gastric and pancreatic fistulas we compared the action of different doses (20.25 to 81.0 nmol/kg/h) of the muscarinic M1-receptor antagonist telenzepine, the cholecystokinin (CCK) antagonist loxiglumide (2.5 to 10.0 mg/kg/h) and several combinations of both drugs on the pancreatic secretory response to intraduodenal perfusion of graded loads of tryptophan (0.37-10.0 mmol/h) given against a background of secretin (20.5 pmol/kg/h i.v.). Except for 20.25 nmol/kg/h telenzepine, all tested doses of telenzepine and/or loxiglumide decreased the 180-min integrated bicarbonate response to tryptophan by 55 to 119%. Except of 20.25 nmol/kg/h telenzepine and/or 2.5 mg/kg/h loxiglumide, all tested doses of telezepine and/or loxiglumide inhibited the tryptophan stimulated integrated pancreatic protein responses by 54 to 88%. While telenzepine mainly inhibited the bicarbonate and protein response to the lower loads of tryptophan (0.37-1.1 mmol/h), loxiglumide decreased the response to all loads of tryptophan. The inhibition evoked by the combinations of telenzepine and loxiglumide was not significantly greater than that by single infusion of either drug. The CCK plasma levels basally and in response to tryptophan were not significantly altered by telenzepine and/or loxiglumide. These findings indicate that (1) both enteropancreatic cholinergic reflexes and the hormone CCK are mediators of the protein response to intraduodenal trytophan (2) enteropancreatic cholinergic reflexes are probably the dominant mediators of the response to low amounts of tryptophan, whereas CCK is the major mediator of the response to high loads of tryptophan, (3) the two mediators seem to act independently of each other, and (4) the release of CCK by intestinal trytophan is not influenced by telenzepine or loxiglumide.

Inhibition of canine exocrine pancreatic secretion by peptide YY is mediated by PYY-preferring Y2 receptors.

It is still unclear, which receptor subtype, Y1 and/or Y2, mediates the inhibitory action of PYY on exocrine pancreatic secretion. The present study was undertaken to characterize functionally the Y receptor subtype that mediates the inhibition of exocrine pancreatic secretion by peptide YY (PYY). In eight conscious dogs with chronic gastric and pancreatic fistulas, we compared the action of intravenous infusion of 200 and 400 pmol/kg/h of the Y receptor agonists PYY 1-36, PYY 3-36, PYY 13-36, Pro34PYY 1-36, and NPY 1-36 on the pancreatic secretory response to secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). PYY 13-36, Pro34PYY 1-36, and NPY 1-36 were also studied by giving a fivefold dose (1,000 and 2,000 pmol/kg/h). PYY 1-36 and the Y2 receptor agonist PYY 3-36 significantly inhibited pancreatic secretory responses to secretin and cerulein, whereas inhibition by NPY 1-36 and the Y2 receptor agonist PYY 13-36 was attainable only at doses of 1,000 and 2,000 pmol/kg/h. The Y1 receptor agonist Pro34PYY 1-36 was without effect on pancreatic secretion. We conclude that in dogs the inhibition of exocrine pancreatic secretion by PYY is mediated via Y2 receptors of a PYY-preferring subtype.

[Neurohormonal control of exocrine pancreas secretions by intra-ileal and intracolonic nutrients]. / Neurohormonale Kontrolle der exokrinen Pankreassekretion durch intraileale und intrakolonische Nährstoffe.

While the duodenum controls pancreatic exocrine secretion mainly via stimulatory mechanisms, intraileal and intracolonic nutrients have mainly inhibitory effects on the postprandial and interdigestive pancreatic secretion, which are described in particular. The inconsistent findings in dogs in contrast to other species (cat, rat, human) referring to the effects of intraileal nutrients are discussed. Possible mechanisms for the neurohormonal mediation of the effects of intraileal and intracolonic nutrients on the pancreatic secretion as well as the possible physiological importance of these effects are discussed.

[Effects of peptide YY on functions of the gastrointestinal tract]. / Die Wirkungen von Peptid YY auf Funktionen des Gastrointestinaltraktes.

The present report gives a review about the localization, release and gastrointestinal actions of peptide YY in different animal species and in humans. Possible mechanisms of action, the physiological and pathophysiological significance of peptide YY and the role of peptide YY 3-36 are discussed. Finally, unanswered questions are specified.

[Acute pancreatitis - association with a Campylobacter coli-infection]. / Campylobacter coli-assoziierte akute Pankreatitis.

A 37-year-old male presented with intermittent abdominal pain and 9 kg weight loss within 3 weeks. Gastroscopy showed no pathological findings, coloscopy showed a colitis limited to the left flexure. Histology revealed a sustained infectious enterocolitis. A culture of the patient's stool was positive for CAMPYLOBACTER COLI. Because of the recurrent abdominal discomfort and weight loss the patient was admitted to the hospital. Ultrasound and multislice spiral computed tomography showed an acute oedematous pancreatitis. No other causes for the pancreatitis were found, the only remaining possibility was a CAMPYLOBACTER COLI-associated pancreatitis. Under symptomatic therapy the patient recovered definitively. An administration of antibiotics was not necessary.

Effects of M1 and CCK antagonists on latency of pancreatic amylase response to intestinal stimulants.

In six conscious dogs with gastric and duodenal cannulas, secretin (164 pmol. kg(-1). h(-1) iv) was given to provide a flow of pancreatic juice of approximately 1 drop/s. Amylase activity was measured in each drop before and after rapid intravenous injection of caerulein (7.4 pmol/kg) or intraduodenal injection of L-tryptophan (1 mmol), sodium oleate (3 mmol), and HCl (3 mmol). All experiments were repeated in the presence of the M1 receptor antagonist telenzepine (81 nmol. kg(-1). h(-) iv) and the cholecystokinin (CCK) receptor antagonist L-364718 (0.1 mg/kg iv). Latency of amylase response (time between injection of stimulant and sustained increase in amylase activity greater than mean + 3 SD of prestimulatory activity) to tryptophan (17 +/- 7 s; n = 6) and oleate (16 +/- 5 s) was significantly (P < 0.05) shorter than to caerulein (28 +/- 4 s) and HCl (120 +/- 47 s). Telenzepine significantly increased the latency of amylase response to tryptophan and oleate by >10-fold but not the latency to caerulein or HCl. L-364718 abolished the amylase response to all stimulants. These findings indicate that the early amylase response to intraduodenal tryptophan and oleate is mediated by a neural enteropancreatic reflex ending on M1 receptors rather than by hormone release. However, the activation of (possibly vagal) CCK receptors is essential to run the reflex. The early amylase response to intraduodenal HCl is probably mediated by the release of CCK into the blood circulation.

Influence of the M1-receptor antagonists telenzepine and pirenzepine on pancreatic secretory response to intraduodenal tryptophan in dogs.

In conscious dogs with gastric and pancreatic fistulas, we compared the action of different doses of telenzepine (ranging from 9 to 243 nmol kg-1 h-1 i.v.) and pirenzepine (ranging from 43 to 1,170 nmol kg-1 h-1 i.v.) on the pancreatic secretory response to graded loads of intraduodenal infusions of tryptophan, given with a secretin background. Both, telenzepine and pirenzepine caused an overall significant inhibition of the cumulative incremental pancreatic protein output by 65.8 and 66.8%, respectively. The pancreatic bicarbonate output was also reduced by 38.3 and 40.5%, respectively, but the effect did not reach statistical significance. The inhibitory potency of the effective doses of telenzepine or pirenzepine did not differ significantly. Only the highest doses of telenzepine (243 nmol kg-1 h-1 i.v.) and of pirenzepine (1,170 nmol kg-1 h-1 i.v.) significantly increased heart rate from 59.9 +/- 3.4 to 63.1 +/- 4.5 bpm, respectively. These findings indicate that (1) in the intact animal, the M1-receptor antagonists telenzepine and pirenzepine are capable of inhibiting pancreatic bicarbonate and protein output in response to intraduodenal tryptophan with secretin background, and (2) telenzepine is 4.7 times more potent than pirenzepine.

Action of beer and its ingredients on gastric acid secretion and release of gastrin in humans.

The intragastric action of beer and its known ingredients before and after fermentation on gastric acid secretion and release of gastrin was studied in healthy humans. None of 11 tested ingredients of fermented beer (2 x 500 mL, pH 5.5, given either alone or in combination) or hop extract had any significant effect. Finished beer (6 weeks old) and new beer were potent stimuli of acid output, causing 93% and 76% of the incremental maximal acid output in response to pentagastrin (6 micrograms/kg SC), respectively. Before the addition of yeast, preproducts of beer were considerably less potent. Thus, first and finished wort caused only a minor acid response which was 48% and 46% of maximal acid output. Foreign fermentation in first and finished wort is presumably the reason for the stimulatory action because glucose solutions in concentrations (11.5% wt/vol) seen in wort did not stimulate acid secretion. However, glucose solutions to which yeast was added, resulting in fermentation, were as potent stimuli of acid secretion as beer. Lyophilization of beer at pH 11.0 and dialysis (cutoff mol wt, 1000) removed the stimulatory substances. The plasma gastrin responses paralleled the gastric acid response to the different stimulants. It was concluded that (a) the addition of yeast to finished wort and the following alcoholic fermentation are the essential steps for the stimulatory action of beer on gastric acid secretion and release of gastrin; (b) carbohydrate metabolites with a molecular weight of less than 1000 are the acid-stimulatory agents in fermented beer; and (c) gastrin is the mediator of the stimulation of acid secretion because all substances that had a potent acid-stimulatory action also were potent stimuli of gastrin release.

Pancreatic exocrine studies in intact animals: historic and current methods.

This report presents a review of the historic and current methods for performing pancreatic exocrine studies in intact animals. Special emphasis is given to the various surgical procedures--pancreatic fistulas, duodenal pouches, and duodenal fistulas--and practice of collecting pancreatic secretion in dogs. Procedures in other animal species--rat, cat, pig, rabbit, cattle, sheep, and horse--also are specified. The advantages and disadvantages, as well as the indications and limitations of the distinct methods, are discussed.

Effect of ethanol and some alcoholic beverages on gastric emptying in humans.

BACKGROUND: There is a paucity of detailed and controlled studies on the action of ethanol and alcoholic beverages on gastric emptying in humans. This study was designed to compare the effect of beer, red wine, whisky and their comparable pure ethanol solutions on gastric emptying in a controlled and randomized investigation. METHODS: On separate days, 10 healthy, fasted subjects received the following solutions, in random order, through a gastric tube: 500 mL beer, red wine, comparable pure ethanol solutions (4% and 10% v/v), glucose (5.5% and 11.4% w/v) and water, 125 mL whisky and 40% (v/v) ethanol (both followed by 125 mL water) and 250 mL water. Gastric emptying of the test solutions was assessed using ultrasonography of the antrum. RESULTS: As measured by ultrasonography of the antrum, half emptying times of the ethanol solutions (4%, 10% and 40% v/v) were significantly (P < 0.05) longer (22.6 +/- 4.8, 22.7 +/- 4.3 and 27.8 +/- 3.3 min, respectively, n=10) than those of water (14.6 +/- 1.9 min (500 mL) and 13.2 +/- 1.7 min (250 mL), respectively). The half emptying times of beer (39.3 +/- 4.3 min) and red wine (72.6 +/- 7.6 min) were significantly longer than those of the corresponding ethanol concentrations, whereas whisky was emptied at nearly the same rate (26.4 +/- 5.9 min) as 40% (v/v) ethanol. Emptying of glucose 5.5% and 11.4% (w/v) was significantly and dose dependently slower (29.7 +/- 4.5 and 64.8 +/- 8.9 min) than water. CONCLUSIONS: 1) Pure ethanol in concentrations of 4%, 10% and 40% (v/v) inhibits gastric emptying. 2) The inhibitory effect of beer and red wine, but not of whisky, is stronger than that of their comparable ethanol concentrations. 3) Caloric content and non-alcoholic ingredients in alcoholic beverages produced by fermentation (beer and wine), but not in those produced by distillation (whisky), are most likely responsible for this effect.

Alcohol and gastric acid secretion in humans.

The secretory response of gastric acid to pure ethanol and alcoholic beverages may be different because the action of the non-ethanolic contents of the beverage may overwhelm that of ethanol. Pure ethanol in low concentrations (< 5% vol/vol) is a mild stimulant of acid secretion whereas at higher concentrations it has either no effect or a mildly inhibitory one. Pure ethanol given by any route does not cause release of gastrin in humans. Alcoholic beverages with low ethanol content (beer and wine) are strong stimulants of gastric acid secretion and gastrin release, the effect of beer being equal to the maximal acid output. Beverages with a higher ethanol content (whisky, gin, cognac) do not stimulate gastric acid secretion or release of gastrin. The powerful stimulants of gastric acid secretion present in beer, which are yet to be identified, are thermostable and anionic polar substances. The effect of chronic alcohol abuse on gastric acid secretion is not as predictable. Chronic alcoholic patients may have normal, enhanced, or diminished acid secretory capacity; hypochlorhydria being associated histologically with atrophic gastritis. There are no studies on the acute effect of alcohol intake on gastric acid secretion in chronic alcoholic patients. The acid stimulatory component of beer and wine needs to be characterised and its possible role in the causation of alcohol induced gastrointestinal diseases needs to be investigated.

[Neurohormonal control of gallbladder motility by intra-ileal and intracolonic nutrients--a review]. / Neurohormonale Kontrolle der Gallenblasenmotilität durch intraileale und intrakolonische Nährstoffe--Ubersichtsreferat.

The duodenum controls gallbladder motility mainly via stimulatory mechanisms, whereas intraileal and intracolonic nutrients have mainly inhibitory effects on postprandial as well as interdigestive gallbladder motility, which are described in particular. Possible mechanisms for the neurohormonal mediation of the effects of intraileal and intracolonic nutrients on gallbladder motility as well as the possible physiological importance of these effects are discussed.

[Effect of 8-week administration of enalapril plus additional 2-week administration of furosemide on heart rate and exocrine pancreas secretion in dogs]. / Wirkung einer 8-wöchigen Dauergabe von Enalapril plus anschliessender zusätzlicher 2-wöchiger Furosemidgabe auf die Herzfrequenz und die exokrine Pankreassekretion des Hundes.

Alteration of pancreatic secretion could be a pathogenetic factor for generation of an acute pancreatitis after administration of angiotensin-converting-enzyme (ACE) inhibitors. Therefore in 6 conscious dogs (weight 10-12 kg) with chronic gastric and duodenal fistulas according to Thomas, we studied single-blind, placebo-controlled and randomized the effect of a long-term (74 d) daily oral administration of 5 mg of the ACE inhibitor enalapril and of additionally daily oral administration of the diuretic furosemide from the 60th day on the secretin- (20.5 pmol/kg/h) and caerulein- (7.4, 14.8, 29.6, 59, and 118 pmol/kg/h) stimulated pancreatic bicarbonate and protein secretion at day 1, 29, 57, 60, and 74 after beginning of enalapril administration. Heart rate was measured daily and during the experiments. Neither enalapril nor enalapril plus furosemide significantly altered heart rate. The hormonally stimulated pancreatic bicarbonate secretion was significantly (p < 0.05) increased at day 57, 60, and 74 by 353%, 397%, and 79%. The hormonally stimulated pancreatic protein secretion was also distinctly increased, although not reaching statistical significance. The present study shows, that a long-term administration of therapeutic doses of enalapril +/-furosemide is capable to enhance the pancreatic bicarbonate secretion. Whether this altered pancreatic secretion can be taken for a primary origin of the observed cases of acute pancreatitis after therapeutic administration of enalapril is uncertain but not refutable.

Action of ethanol and some alcoholic beverages on gastric acid secretion in anaesthetized rats.

The action of intragastric ethanol in various concentrations equivalent to those found in alcoholic beverages (1.5-40 v/v), ethanol 96% (v/v) and of some commonly ingested alcoholic beverages produced by alcoholic fermentation (beer, wine, champagne, martini and sherry) or by fermentation plus distillation (e.g. whisky, cognac, calvados, armagnac and rum) on gastric acid output (GAO) was studied in anaesthetized Wistar rats. Ethanol concentrations of 1.5%, 4% and 10% v/v did not significantly alter basal GAO, whereas all higher concentrations of ethanol (20%, 40% and 96% v/v) significantly (P < 0.05) and dose-dependently decreased the GAO. All alcoholic beverages produced by fermentation significantly increased GAO by 30-35% of maximal acid output (MAO; 48 micrograms/kg pentagastrin intramuscularly), whereas alcoholic beverages produced by fermentation plus distillation significantly decreased GAO as compared to control (isotonic glucose and distilled water). Glucose solutions to which yeast was added, resulting in fermentation, were as potent stimuli of GAO as beer. Lyophilized fermented glucose at different concentrations (dilution of 1:20 to 1:1) dose-dependently stimulated GAO: the highest dilution (1:20) had no effect, the 1:5 dilution significantly increased gastric acid secretion similarly to that of beer and fermented glucose. The highest concentration of lyophilized fermented glucose (1:1) was as potent as the MAO after pentagastrin (90% of MAO). In conclusion, the present investigation shows for the first time that, in rats: (1) ethanol in a concentration > 10% v/v inhibits GAO; (2) lower ethanol concentrations (< 10% v/v) do not alter GAO; (3) alcoholic beverages produced by fermentation but not those produced by alcoholic fermentation plus distillation are powerful stimulants of GAO; (4) the stimulatory non-alcoholic ingredients of these alcoholic beverages are most likely produced during the process of fermentation of carbohydrates and removed during the following process of distillation.