Wojciech Obtułowicz

Effect of growth hormone-release inhibiting hormone on hormones stimulating exocrine pancreatic secretion.

The nature and extent of growth hormone-release inhibiting hormone (GH-RIH, somatostatin)-induced inhibition of pancreatic secretion of bicarbonate and protein, an index of enzyme secretion, were studied by administration of exogenous secretin or cholecystokinin (CCK) and of a number of stimulants for endogenous release of these hormones in fasted pancreatic fistula dogs with and without an infusion of GH-RIH. The results of this study show that GH-RIH inhibits the pancreatic fluid and bicarbonate secretion induced by duodenal acidification and exogenous secretion. The kinetic analysis shows that the interaction between GH-RIH and secretin affecting pancreatic bicarbonate secretion possesses the characteristics of competitive inhibition. GH-RIH does not change the pancreatic protein response to exogenous CCK, but profoundly inhibits pancreatic response to a variety of the endogenous stimulants of CCK release, including duodenal perfusion of sodium oleate, amino acid mixture, or feeding of a peptone meal. We conclude that GH-RIH is a very potent inhibitor of the endogenous release of CCK from the intestinal mucosa and inhibits competitively the action of secretin but not CCK on the exocrine pancreatic secretion.

Effect of atropine on pancreatic responses to endogenous and exogenous cholecystokinin

The role of cholinergic innervation in endogenous release of cholecystokinin from the intestinal mucosa and in exocrine pancreatic secretion was examined by means of atropine administration in 3 chronic gastric-fistula and pancreatic-fistula dogs during pancreatic responses to various rates of intraduodenal amino acid mixture and to various doses of intravenous cholecystokinin producing equal rates of pancreatic protein secretion. Atropine infused in a dose of 100 µg/kg-hr caused a deep and prolonged decrease in pancreatic flow rate, protein and bicarbonate output, reaching a maximum of about 80% of the pre-atropine level of pancreatic secretion. The inhibition occurred regardless of the level of pancreatic response examined. Atropine also caused an inhibition of pancreatic responses to smaller doses of exogenous cholecystokinin but did not affect responses to larger doses. The maximal observed pancreatic protein secretion in response to intraduodenal administration of amino acids was about 80% of the highest response to cholecystokinin. This study suggests that the release of cholecystokinin from the intestinal mucosa might be cholinergically dependent.

Oral cavity as a potential source of gastric reinfection by Helicobacter pylori

Helicobacter pylori (Hp) is a common pathogen colonizing the a gastric mucosa, but some reports indicated that it may also be found in the oral cavity, which could serve as a reservoir of the bacteria and a source of gastric reinfection. Accordingly, we aimed to study whether the oral cavity, particularly gingival pockets, are colonized by Hp and whether it could be the source of gastric reinfection. We studied 329 patients with dyspeptic symptoms (257 with chronic gastritis, 15 with gastric ulcer, and 57 with duodenal ulcer). The [13C]urea breath test (UBT), gastroscopy, and Hp culture from gastric biopsies were carried out, and material was collected from the oral cavity (gingival pocket) for bacteriological culture and genomic DNA studies. The serum was obtained for anti-Hp IgG and anti-CagA assays and saliva for anti-Hp IgA determination using the ELISA technique. Bacteria in material from gingival pockets and biopsies from the corpus and antrum of stomach of 30 DU patients before and after Hp eradication were also examined by PCR technique, using primers specific for 16S rRNA. All Hp-positive patients (276) were subjected to one week of triple therapy (omeprazole 2 × 20 mg twice a day, clarithromycin 2 × 500 mg twice a day, and metronidazole 2 × 500 mg twice a day). The measurements described above were then repeated at four weeks and six months. Bacteriological culture showed the presence of Hp in the material from oral cavity in about 50% of patients, whereas UBT, used as a gold standard, revealed gastric Hp infection in about 84% of these patients. The eradication was successful in the majority of patients (87%), but about 13% of them were still Hp positive after four weeks and about 21% after six months. Four weeks after Hp therapy, Hp was found in culture from oral samples in 23% (P < 0.05 vs initial) and after six months in 35.1%. The IgA levels recorded in saliva were in a close agreement with UBT results. Hp DNA assessed by PCR in 30 DUs before eradication of Hp was detected in 95% of antral mucosa, 90% in corpus mucosa, and in 35% of gingival pocket material, and after eradication therapy Hp DNA values fell to 25%, 20%, and 10%, respectively. In conclusion, Hp is commonly detected in the oral cavity of patients with dyspeptic symptoms, but the gastric reinfection does not appear to occur in the patients despite oral Hp colonization.

Effect of Metiamide, a Histamine H2-Receptor Antagonist, on Mucosal Blood Flow and Serum Gastrin Level

In dogs with gastric fistulae and vagally denervated Heidenhain pouches, metiamide, a histamine H2-receptor antagonist, infused intravenously in a dose of 12 μmoles per kg-hr, inhibited near maximal acid responses to histamine, pentagastrin, Urecholine, or a peptone meal. Atropine sulfate (0.12 μmole per kg-hr) did not significantly affect acid output induced by histamine, but was a more effective inhibitor of acid secretion stimulated by pentagastrin, Urecholine, or a peptone meal. Serum gastrin response to a peptone meal was unchanged by metiamide but partly suppressed by atropine. The inhibitory effect of metiamide was always associated with a marked reduction in mucosal blood flow. The ratio of aminopyrine concentration in the gastric juice and blood plasma was not significantly changed by metiamide, indicating that the persistent reduction in gastric mucosal blood flow was secondary to an inhibition of gastric secretion.

Characteristics of Inhibition of Pancreatic Secretion by Glucagon

The inhibition of cholecystokinin (CCK)-induced pancreatic secretion by glucagon was studied in four dogs with chronic pancreatic fistulas and open gastric fistulas. After establishing a constant level of secretion by intravenous infusion of CCK at a constant rate (doses: 3, 6, 12 and 24 U/kg/h) glucagon was given by constant intravenous infusion for 1 h in constant doses (6, 12, 25 and 50 μg/kg/h). From the dose response curves to CCK alone and CCK plus 25 μ/kg/h glucagon, the Michaelis-Menten analysis was typical of competitive inhibition, i.e., the calculated maximal response was similar and the dose required for half maximal response was different. Glucagon also inhibited pancreatic secretion elicited by intraduodenal instillation of a solution of L-tryptophan and L -leucine. It was concluded that glucagon inhibits the CCK-stimulated pancreatic secretion in the dog and that this inhibition is competitive.

COMPARISON OF AMINO ACIDS BATHING THE OXYNTIC GLAND AREA IN THE STIMULATION OF GASTRIC SECRETION

This study was undertaken to compare the ability of L- and D-isomers of amino acids bathing the oxyntic gland area to stimulate acid secretion in conscious dogs with Heidenhain pouch (HP), gastric fistula (GF) and pancreatic fistula (PF). Acid outputs from HP were determined by an intragastric titration method when amino acid solutions were perfused into HP at various concentrations, pH values, and distention pressures. Only L-isomers of all natural amino acids were found to stimulate acid secretion, whereas D-isomers of amino acids tested were completely inert in this respect. The comparison of the secretagogue activity of amino acids shows that L-histidine among essential amino acids and glycine among nonessential amino acids exhibited the strongest stimulation of acid outputs, reaching, respectively, 52 and 40% of the maximal response to histamine. Decreasing the pH of L-histidine solution perfused into HP in sequential order from 5.0 to 1.0 resulted in a stepwise reduction of acid output, falling at pH 1.0 to about 40% of the peak response achieved at pH 5.0. Local irrigation of HP by 2% xylocaine and intravenous infusion of atropine (100 mug per kg per hr) or metiamide (2.9 mg per kg per hr) reduced but did not abolish HP response to chemical stimulation and the pH dependency of this response. We conclude that only L- and not D-isomers of amino acids bathing the oxyntic gland area stimulate acid secretion by a local, gastrin-independent mechanism sensitive to distention pressure and pH.

Effect of ranitidine, a new H2-antagonist, on gastric and pancreatic secretion in duodenal ulcer patients

The effects of a new H2-receptor blocker, ranitidine, given intravenously (for comparison with cimetidine) or orally on gastric and pancreatic secretion have been studied in duodenal ulcer patients. Ranitidine appears to be several times more potent and a longer-acting inhibitor of gastric secretion than cimetidine. This H2 blocker does not affect pancreatic bicarbonate and enzyme secretion.

Effect of atropine on pancreatic responses to endogenous and exogenous secretin

The role of cholinergic innervation in endogenous release of secretin from the intestinal mucosa, and in exocrine pancreatic secretion was examined by means of atropine administration in 4 chronic gastric-fistula and pancreatic-fistula dogs during pancreatic response to various doses of synthetic secretin and to various rates of intraduodenal acid load. Atropine infused in a dose of 100µg/kg/hr caused a deep and prolonged decrease of pancreatic flow rate and bicarbonate output reaching a maximum of about 70% of the pre-atropine level of pancreatic secretion. The inhibition occurred regardless of the level of pancreatic response examined, and no significant difference between the effects of atropine on pancreatic responses to exogenous and endogenous secretin was found. Intraduodenal infusion of atropine caused significantly greater inhibition of the pancreatic response to intestinal acidification than that to exogenous secretin. This suggests that release of secretin from the intestinal mucosa might be under the cholinergic control of local nerves.

Luminal Nα-methyl histamine stimulates gastric acid secretion in duodenal ulcer patients via releasing gastrin

Nalpha-methyl histamine is an unusual histamine metabolite which is produced in the stomach infected by Helicobacter pylori and which was shown in animals to stimulate gastric acid secretion and to release gastrin in vitro isolated G-cells, but no information is available regarding its influence on gastric secretion and gastrin release in duodenal ulcer patients before and after H. pylori eradication. In this study, we compared the effects of intragastric administration of single or graded doses of Nalpha-methyl histamine on gastric acid secretion and plasma gastrin levels in 16 male duodenal ulcer patients (aging from 35 to 48 years and weighing 65-82 kg) before and after the eradication of H. pylori. Furthermore, the gastric luminal histamine and gastrin contents were determined before and after H. pylori eradication. In H. pylori-infected duodenal ulcer patients, the intragastric application of Nalpha-methyl histamine failed to affect gastric acid secretion or plasma gastrin levels. Following eradication of H. pylori, gastric luminal histamine and gastrin, and both basal gastric acid secretion and plasma gastrin levels, were significantly reduced. Nalpha-methyl histamine given intragastrically in graded doses to such H. pylori-eradicated duodenal ulcer patients was found to increase dose-dependently gastric acid output reaching at a dose of 5 mg, about 80% of histamine maximum induced by i.v. infusion of 25 microg/kg h of histamine dihydrochloride. We conclude that Nalpha-methyl histamine is a potent luminally active stimulant of gastrin release and gastric acid secretion in H. pylori-eradicated patients when luminal histamine is low but is not effective in H. pylori infected patients when luminal histamine is enhanced, possibly due to desensitization of gastrin (G-cells) and acid-producing (parietal) cells by Nalpha-methyl histamine produced excessively in H. pylori-infected stomach.

Effect of Glucagon on Food-Induced Gastrointestinal Secretions

The action of glucagon on gastrointestinal secretion has been studied in two groups of 3 dogs each. The group-A dogs were prepared with gastric fistulas, Pavlov pouches and pancreatic fistulas, while the dogs in group B possessed only gastric fistulas and biliary fistulas. Glucagon infused intravenously in a dose of 25 μg/kg-h, during a steady state of half maximal secretory response to food caused a marked inhibition of acid secretion from Pavlov pouches and bicarbonate and protein secretion from pancreatic fistula. Biliary secretion was not affected by glucagon.