The effects of ammonia on pancreatic enzyme secretion in vivo and in vitro.

Background: Recent studies clearly demonstrate that Helicobacter pylori (H. pylori) infection of the stomach causes persistent elevation of ammonia (NH3) in gastric juice leading to hypergastrinemia and enhanced pancreatic enzyme secretion.

Methods: The aim of this study is to evaluate the influence of NH4OH on plasma gastrin level and exocrine pancreatic secretion in vivo in conscious dogs equipped with chronic pancreatic fistulas and on secretory activity of in vitro isolated acini obtained from the rat pancreas by collagenase digestion.

Role of endogenous nitric oxide in the control of gastric acid secretion, blood flow and gastrin release in conscious dogs.

Nitric oxide (NO) was shown to mediate gastric hyperemia following secretory stimulation but its role in the control of gastric secretion has not been clarified. Secretory studies were carried out on conscious dogs with chronic gastric fistula, Heidenhain pouch and esophageal fistula, while changes in gastric blood flow were measured in the mucosa of Heidenhain pouuch by laser Doppler flowmetry. Plasma gastrin was determined by radioimmunoassay.

Antagonism of receptors for gastrin, cholecystokinin and GRP/bombesin in postprandial stimulation of exocrine pancreas in dogs.

Postprandial pancreatic secretion results from the interaction of neural and hormonal factors such as cholecystokinin (CCK), gastrin and gastrin releasing peptide (GRP), but their contribution to the net secretion is not established. Recent description of highly specific and potent hormonal receptor antagonists allows the determination of the physiological role of CCK, gastrin and GRP. In six dogs with chronic pancreatic fistulas, the blockade of CCK receptors by L-364, 718, gastrin receptors by L-365, 260 or GRP/bombesin receptors by nonapeptide RC-3095 failed to affect basal or sham-feeding induced pancreatic secretion indicating that none of these hormonal peptides plays a major role in this secretion.

Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow.

Background: Endogenous nitric oxide has been implicated in the control of mesenteric circulation, but its role in the control of pancreatic blood flow and exocrine pancreatic secretion has not been studied.

Methods: Secretory studies were performed on conscious dogs with chronic pancreatic fistulas, and changes in pancreatic blood flow were measured by laser Doppler flowmetry in anesthetized animals.

Results: Infusion of NG-nitro-L-arginine did not affect basal pancreatic protein secretion but suppressed an increase of this secretion induced by L-arginine but not that induced by glyceryl trinitrate.

Role of cholecystokinin in the intestinal fat- and acid-induced inhibition of gastric secretion.

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%.

Role of cholecystokinin in the inhibition of gastric acid secretion in dogs.

1. This study was designed to determine the involvement of cholecystokinin (CCK) in the gastric secretory responses to exogenous and endogenous secretagogues in conscious dogs with chronic gastric fistulae (GF), pancreatic fistulae (PF) and Heidenhain pouches (HP). 2.

Role of liver and intestines in the degradation of epidermal growth factor.

Epidermal growth factor (EGF) is widely distributed in the gastrointestinal tissues and released into the gut lumen but its physiological role is questionable because of the postulated high uptake and degradation of this peptide in the liver. This study was designed to examine the action of EGF administered intraduodenally (i.d.

Effects of non-peptidal CCK receptor antagonist (L-364,718) on pancreatic responses to cholecystokinin, gastrin, bombesin, and meat feeding in dogs.

Postprandial pancreatic secretion results from the interaction of neural and hormonal factors but their contribution to the net postprandial secretion is unknown. Recent description of highly specific and potent cholecystokinin (CCK) receptor antagonists allows the determination of the physiological role of CCK in the postprandial pancreatic secretion. In six dogs with chronic pancreatic fistulae, the blockade of CCK receptors by non-peptidal agent (L-364,718) caused little change in basal pancreatic secretion, but decreased significantly (p less than 0.

Comparison of telenzepine, pirenzepine and atropine on gastric acid and pepsin secretion in response to histamine, pentagastrin, bethanechol, sham-feeding and feeding.

This study was designed to compare gastric antisecretory effects of telenzepine, a new antimuscarinic agent, with those of pirenzepine and atropine in dogs. None of these antimuscarinics affected gastric acid secretion induced by histamine but all of them caused a dose-dependent inhibition of acid secretion from the gastric fistula (GF) and Heidenhain pouches (HP) stimulated by pentagastrin and bethanechol, telenzepine being 5-9 times more potent than pirenzepine and equipotent with atropine. All antimuscarinics were also effective inhibitors of acid responses to sham feeding and ordinary feeding.

Effect of cholecystokinin receptor antagonist on pancreatic responses to exogenous gastrin and cholecystokinin and to meal stimuli.

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.

Cephalic phase of gastroduodenal alkaline secretion.

Alkaline secretion measured under basal conditions in the intact stomach of conscious dogs averaged 47 mumol/30 min and was about twice lower than that recorded in the proximal (approximately 7 cm long) portion of the duodenum. Vagal excitation elicited by sham feeding and insulin resulted in a marked stimulation of alkaline secretion both from the stomach and the duodenum. Atropine significantly reduced gastric and duodenal alkaline secretion under basal state.

Subtypes of muscarinic receptors in canine pancreatic secretion in vivo and in vitro.

In conscious dogs with esophageal, gastric and pancreatic fistulae, sham-feeding and meat feeding increased the pancreatic protein secretion to a peak, reaching about 39% and 69% of CCK8 maximum, and raised plasma pancreatic polypeptide (PP) levels. Pirenzepine given intravenously (i.v.

Comparison of gastric inhibitory polypeptide and intraduodenal or intravenous fat on gastric acid secretion from vagally innervated and denervated canine stomach.

Gastric inhibitory polypeptide (GIP), given to dogs in graded doses (range 0.25-2 micrograms/kg/hr) against a constant background stimulation with pentagastrin (4 micrograms/kg/hr), failed to affect the acid secretion at all doses used except the largest one (2 micrograms/kg/hr) which significantly reduced the acid secretion only from the vagally denervated portion of the stomach (Heidenhain pouch, HP) while raising plasma GIP two to three times above the levels reached with duodenal fat. GIP infused in a constant dose (1 microgram/kg/hr) significantly reduced the HP responses to lower (0.

Cephalic phase of gastroduodenal alkaline secretion.

This study was designed to determine gastric alkaline secretion (GAS) and duodenal alkaline secretion (DAS) and their relation to the duodenal motility pattern in conscious dogs under basal conditions and after vagal stimulation by sham-feeding and insulin hypoglycaemia. GAS was measured in the gastric perfusate and DAS was determined in the perfusate of the upper duodenum (7 cm in length between occluding balloons). Resting GAS and DAS showed typical periodicity in phase with myoelectric and motor activity, reaching peaks during phases II and III, respectively, and nadir during phase I of the migrating motor cycle (MMC).

Effects of cyclic hexapeptide analog of somatostatin on pancreatic secretion in dogs.

The effects of a cyclic hexapeptide analog of somatostatin, [cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe)] (cyclo-SS), administered intravenously (iv) or instilled into the duodenum (id) on the pancreatic response to endogenous (meal and duodenal acidification) and exogenous (secretin, CCK) stimulants were compared in five dogs with esophageal, gastric, and pancreatic fistulae. Cyclo-SS given iv in graded doses against a constant background stimulation with secretin caused a similar and dose-dependent inhibition of pancreatic HCO3 and protein secretion being about twice as potent as somatostatin-14 (SS-14). Cyclo-SS, whether applied topically to the duodenal mucosa in a dose of 1 microgram/kg or given iv at a dose of 0.

Effects of epidermal growth factor on gastrointestinal secretions.

Epidermal growth factor (EGF) has been reported to stimulate epithelial cell proliferation and to inhibit gastric H+ secretion, but no details of the latter effect have been studied. This paper reports the effects of EGF on gastric and pancreatic secretions induced by various stimulants in vivo on conscious dogs and in vitro on isolated rabbit gastric glands. EGF was found to be an effective inhibitor of H+ secretion induced from the fully innervated and vagally denervated portions of the stomach stimulated by secretagogues activating receptors of the parietal cells (pentagastrin, histamine, and urecholine) and by natural stimulants such as sham or ordinary feeding.

Effects of omeprazole, a substituted benzimidazole, on gastrointestinal secretions, serum gastrin, and gastric mucosal blood flow in dogs.

In dogs with gastric fistulas and vagally denervated Heidenhain pouches, omeprazole, a benzimidazole derivative infused intravenously or given intraduodenally, dose-dependently inhibited gastric acid secretion, which had been induced by histamine, pentagastrin, or urecholine. It also suppressed gastric acid response to physiologic stimulants such as sham-feeding and gastric peptone meal without affecting serum gastrin level. The inhibition of histamine-induced acid secretion was accompanied by a parallel reduction in the mucosal blood flow, but no significant alteration in the ratio (R) value, indicating that omeprazole primarily affected gastric acid secretion but did not limit gastric mucosal microcirculation.

Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs.

In six conscious dogs with esophageal, gastric, and pancreatic fistulas, the effects of intravenous infusion of neurotensin and intraduodenal instillation of sodium oleate on gastric and pancreatic secretion were determined under basal conditions and after exogenous (secretin and cholecystokinin octapeptides) or endogenous stimulants (feeding and duodenal acidification). Neurotensin given intravenously in graded doses (1.5-200 pmol .

Comparison of enkephalin and atropine in the inhibition of vagally stimulated gastric and pancreatic secretion and gastrin and pancreatic polypeptide release in dogs.

Enkephalins have been detected in vagal nerves and myenteric plexus neurons but no study has been performed to determine their action on vagally stimulated gastric and pancreatic secretion. In this study we infused IV methionine-enkephalin (Met-enk) alone, naloxone (a pure opiate antagonist) alone, or their combination before, during and after vagal stimulation in 4 dogs with esophageal, gastric and pancreatic fistulas. For the comparison, atropine was given before, during and after vagal stimulation in the same animals.

Gastric acid response to topical or intravenous histamine and topical H2-receptor blockade in dogs.

This study was undertaken to determine gastric acid surface and to examine the local effect f ranitidine, a histamine H2-receptor antagonist, on the gastric acid response to histamine. Histamine applied to the Heidenhain pouch (HP) mucosa resulted in a slight and dose-dependent stimulation of acid secretion without affecting acid secretion from the main stomach. Ranitidine given into the HP caused dose-dependent inhibition of the HP response to topical or intravenous histamine without affecting the acid response of the main stomach and without any significant change in the serum ranitidine level.

Pancreatic polypeptide and vagal stimulation of gastric and pancreatic secretion in dogs.

In four dogs provided with pancreatic, gastric, and esophageal fistulae, the effects of bovine pancreatic polypeptide (BPP) infused at a physiological dose level (240 pmol per kg/hr) on gastric and pancreatic responses to sham-feeding were studied. The maximal gastric and pancreatic secretion was produced by pentagastrin and secretin, and OP-CCK infusion, respectively, with or without additions of BBP. Exogenous BPP did not change gastric acid and pepsin outputs stimulated by pentagastrin or sham-feeding, but significantly inhibited basal and maximally stimulated pancreatic protein secretion.

Studies on the inhibition of pancreatic secretion by luminal somatostatin.

The effects of somatostatin, instilled into the duodenum or administered intravenously, on pancreatic response to endogenous (meal and duodenal acidification) or exogenous (secretin and caerulein) stimulants were compared in five dogs with gastric and pancreatic fistulas. Somatostatin, whether applied topically to the duodenal mucosa or given intravenously, resulted in qualitatively similar inhibition of pancreatic secretion of water, bicarbonate, and enzyme protein, being about four to eight times less potent after intraduodenal than after intravenous administration. A meal-induced secretion appears to be the most sensitive to the inhibitory action of intraduodenal somatostatin, probably because of the suppression of gastric acid and serum gastrin secretin involved in the postprandial stimulation of the exocrine pancreas.

Effect of substance P and its C-terminal hexapeptide on gastric and pancreatic secretion in the dog.

In five dogs with gastric fistulas, Heidenhain pouches, and pancreatic fistulas, the effects of substance P (SP) and its C-terminal hexapeptide (SP6-11) on gastric acid and pancreatic secretions were determined under basal conditions and in response to secretory stimulation. SP or SP6-11 infused alone in graded doses (0.25-2.

Effect of pancreatic polypeptide and its C-terminal hexapeptide on meal and secretin induced pancreatic secretion in dogs.

1. Gastric acid and pancreatic bicarbonate and protein secretion as well as immunoreactive serum gastrin and pancreatic polypeptide concentrations in response to a meal and secretin have been measured before and after infusion of bovine pancreatic polypeptide or its C-terminal hexapeptide. 2.