Biomedical subjects

J Tasler

Publications and source records attributed to J Tasler.

At least 37 records · Page 2Linked to original sources

PubMed1986

Role of endogenous prostaglandins in duodenal alkaline response to luminal hydrochloric acid or arachidonic acid in conscious dogs.

Duodenal secretion of HCO-3 and luminal release of PGE2 were measured in conscious dogs. The results show that the HCO-3 secretion is closely correlated with the luminal release of PGE2 and that both the HCO-3 and the PGE2 outputs increase dose-dependently after topical application of hydrochloric acid or arachidonic acid. Indomethacin reduced basal HCO-3 and PGE2 release and prevented their increase in response to hydrochloric acid or arachidonic acid. We conclude that mucosal PGE2 plays an important role in the alkaline secretion from the duodenum.

Animals↗

PubMed1986

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). Vagal excitation by sham-feeding or insulin hypoglycaemia resulted in an immediate rise in GAS and DAS, accompanied by a suppression of MMC. Atropine (25 micrograms/kg) reduced basal GAS and DAS by about 50% and abolished GAS but not DAS in response to vagal stimulation, being accompanied by complete suppression of MMC for several hours. Following injection of indomethacin (2.5 mg/kg) to suppress the generation of endogenous prostaglandins, a prolonged reduction in basal GAS and DAS and an increase in the myoelectric activity and the disruption of the MMC occurred. Neither GAS nor DAS responses to vagal stimulation were affected by indomethacin. We conclude that resting GAS and DAS fluctuate cyclically in phase with gastroduodenal motor activity, and that vagal excitation results in a potent stimulation of alkaline secretion and myoelectric activity which are, in part, cholinergic and do not depend upon the generation of endogenous prostaglandins.

Animals↗

PubMed1985

Gut hormones in stimulation of gastroduodenal alkaline secretion in conscious dogs.

Alkaline secretion from the fundic and antral pouches of the stomach and the loops of proximal and distal duodenum was measured in conscious dogs under basal conditions and after intragastric instillation of HCl solution, meat feeding, or intravenous infusion of various gut hormones. In control tests on fasted dogs HCO-3 output from the duodenal mucosa was severalfold higher than that from the gastric mucosa. Instillation of 10 mM HCl into the stomach resulted in a significant increment in HCO-3 secretion from the gastric pouches and proximal duodenal loops, and this was accompanied by a marked increase in plasma secretin, cholecystokinin (CCK), and pancreatic polypeptide (PP) levels. Meat feeding stimulated HCO-3 secretion from proximal duodenum, and it was accompanied by a significant elevation in plasma gastrin, secretin, CCK, gastric inhibitory peptide, and PP. Among exogenous hormones, the most effective stimulant of HCO-3 secretion was PP, which caused a significant increase in HCO-3 output from the gastric and duodenal mucosa at doses (125-500 pmol X kg-1 X h-1) that raised plasma PP to postprandial levels. CCK in physiological doses (21-85 pmol.kg-.h-1) also stimulated HCO-3 secretion from gastric pouches and proximal duodenal loops. Neurotensin stimulated HCO-3 secretion from both gastric pouches and duodenal loops. In contrast, gastrin or secretin did not affect significantly HCO-3 secretion from the gastroduodenal mucosa. This study provides evidence that some gut hormones, particularly PP, CCK, and neurotensin, may be involved in the physiological stimulation of gastroduodenal alkaline secretion.

Animals↗

PubMed1984

Gastroduodenal alkaline response to acid and taurocholate in conscious dogs.

Alkaline secretion was measured in the fundic and antral portions of the stomach and in the upper and distal portions of the duodenum in conscious dogs under basal conditions, in response to luminal exposure of HCl and taurocholate, and after feeding. Topical application of HCl (6.7-100 mM) resulted in an increase in HCO-3 output, particularly from the upper duodenum, and this was associated with the rise in prostaglandin (PG) E2 release. Since both these effects were abolished by pretreatment with indomethacin, it was concluded that the stimulation of alkaline secretion by topical HCl is mediated by mucosal PGs. HCl instilled into the main stomach or feeding a meat meal also caused an increase in alkaline secretion from the isolated (non-acid-perfused) gastric and duodenal portions, but this effect was not affected by indomethacin, suggesting that it was not mediated by endogenous PGs. Direct exposure of the mucosa to luminal taurocholate (0.62-20 mM) adjusted to pH 6.0 also increased gastroduodenal HCO-3 output, but this effect was not affected by indomethacin and accompanied by a fall in transmucosal PD value, suggesting that it could be due to the damage of the mucosa and increased mucosal permeability to HCO-3. We conclude that gastroduodenal HCO-3 output increases in response to natural substances such as HCl, taurocholate, or feeding, and the mechanism of this increase differs depending on the stimulant used.

Animals↗

PubMed1984

Role of prostaglandins in alkaline secretion from the gastroduodenal mucosa exposed to acid and taurocholate.

Gastroduodenal mucosa produces alkaline secretion (AS) that is several times greater in the duodenum, particularly in its proximal part, than in the fundic or antral portions of the stomach. Exogenous prostaglandins (PGs) of E and F but not of I series are capable of augmenting AS. Similar stimulatory effects on AS were observed after topical administration of arachidonic acid and HCl solution. Endogenous PGs appear to mediate this AS as their release from the mucosa is increased upon exposure to arachidonic acid and the pretreatment with indomethacin reduced the alkaline response to arachidonic acid and HCl. Taurocholate-induced alkaline response is probably due to increased mucosal permeation for HCO3 as it was accompanied by a decrease in PD value and indomethacin failed to affect this response.

16,16-Dimethylprostaglandin E2↗

PubMed1984

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. Omeprazole, infused into the Heidenhain pouch, caused a dose-dependent inhibition of the Heidenhain pouch response to intravenous histamine without any significant change in the acid response of the main stomach and plasma concentrations of the drug. This indicates that omeprazole may exhibit local inhibitory action on the oxyntic glands. Omeprazole did not affect gastric mucosal integrity or the rate of alkaline secretion from the gastroduodenal mucosa or the pancreas stimulated by duodenal acidification or secretin.

Administration, Topical↗

PubMed1983

Prostaglandins and alkaline secretion from oxyntic, antral, and duodenal mucosa of the dog.

Alkaline secretion (AS) measured under basal conditions in oxyntic and antral pouches of conscious dogs averaged about 20 mumol/30 min and was about three times lower than that from the duodenal pouch. Natural prostaglandin E2 and prostaglandin F2 alpha, but not prostaglandin I2, were effective stimulants of AS, mainly when given topically. Stable analogues such as 16,16-dimethyl prostaglandin E2 and prostaglandin I2 were relatively more potent stimulants than their parent prostaglandins (PGs), particularly when applied topically. The highest alkaline response of the oxyntic pouch to PG was about 5% of the maximal acid response of this pouch to histamine. Indomethacin reduced markedly AS from the duodenal but not from the oxyntic or antral pouch. AS from the duodenal pouch was relatively more sensitive than that from gastric pouches to the stimulation by PGs, which were effective also after pretreatment with indomethacin. This study shows that the oxyntic, antral, and duodenal mucosa of conscious dogs is capable of secreting bicarbonate, and this secretion, particularly from the duodenal mucosa, is highly sensitive to the stimulation with certain PGs, mainly of the E and F type and their analogues, and to suppression by indomethacin, a potent inhibitor of PG biosynthesis, suggesting that endogenous PGs are involved in the mechanism of AS.

Animals↗

PubMed1982

Effect of human pancreatic polypeptide and its C-terminal hexapeptide on pancreatic secretion in man and in the dog.

Human pancreatic polypeptide (HPP) and its C-terminal hexapeptide (HP-PP) were infused intravenously in graded doses into healthy human subjects and dogs with chronic pancreatic fistula during submaximal stimulation with secretin. Plasma levels of PP were measured by radioimmunoassay, and pancreatic volume flow and bicarbonate and protein outputs were monitored. PP and HP-PP in humans did not affect secretion-induced volume flow or bicarbonate secretion, but at the highest doses it reduced the protein outputs. In dogs both HPP and HP-PP inhibited dose-dependently the pancreatic volume flow and bicarbonate and protein outputs. There was a linear correlation between the dose of HPP infused and the increments in plasma PP levels in these experiments. The inhibition of pancreatic secretion occurred at doses of exogenous HPP which produced blood plasma PP concentrations not significantly different from those normally seen after a meat meal. We conclude that there is a marked difference in the effect of HPP on the exocrine pancreas in man and the dog, that PP may play a role as a physiological inhibitor of pancreatic protein secretion in man and of both bicarbonate and protein secretion in the dog, and that the effect of HPP on the exocrine pancreas can be mimicked by its C-terminal hexapeptide.

Adult↗

PubMed1981

Comparison of TRH and anorexigenic peptide on food intake and gastrointestinal secretions.

Thyrotropin releasing hormone (TRH), distributed throughout the gastrointestinal tract, and anorexigenic peptide (AP), isolated recently from the urine of females with "hypothalamic" anorexia nervosa, have been shown to affect food intake but no study has been performed to compare their action on gastrointestinal secretions. This report shows that both TRH and AP reduce dose-dependently the food intake during sham-feeding and inhibit gastric and pancreatic secretions in response to various exogenous and endogenous stimulants in conscious dogs. The results indicate that TRH and AP have similar inhibitory action on feeding and gastrointestinal secretory activity and that they may be involved in peptidergic mediation of satiety and gastrointestinal secretion.

Animals↗

PubMed1981

Gastrointestinal secretory, motor, circulatory, and metabolic effects of prosomatostatin.

This study compares the gastrointestinal effects of somatostatin (SS) and its putative prohormone, prosomatostatin (Pro-SS), a 28-amino acid peptide isolated from the hypothalamus and the gut, in conscious dogs with chronic gastric and pancreatic fistulae. Pro-Ss suppressed the release of serum gastrin, insulin, and pancreatic polypeptide that occurs in response to feeding a meat meal in a manner similar to that seen with SS. However, in contrast to SS, which strongly reduced intestinal blood flow and oxygen consumption and stimulated intestinal motility, Pro-SS, at the doses tested, had no influence on mesenteric circulation, oxygen uptake, and intestinal motility. We conclude that Pro-SS mimics most of the gastrointestinal secretory actions of SS, but does not exhibit the intestinal circulatory, metabolic, and motor effects of SS.

Animals↗

PubMed1981

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. Liver extract meal kept in the stomach at pH 5.5 (by intragastric titration) produced a marked increase in gastric acid and pancreatic protein secretion accompanied by a rise in serum gastrin and pancreatic polypeptide levels. Exogenous bovine pancreatic polypeptide caused little change in gastric secretion and serum gastrin but resulted in a profound suppression of pancreatic secretion. 3. Ordinary feeding a liver meal produced a marked increase in pancreatic bicarbonate and protein secretion that was dose-dependently inhibited by bovine pancreatic polypeptide or its C-terminal hexapeptide, the degree of inhibition being closely correlated with the increments in plasma pancreatic polypeptide. 4. Bovine pancreatic polypeptide and its C-terminal hexapeptide also inhibited secretin and caerulein-induced pancreatic secretion in a dose-dependent manner. 5. This study shows that bovine pancreatic polypeptide inhibits pancreatic secretion at least in part by acting directly on the exocrine pancreas and that its biological activity resides in its C-terminal hexapeptide fragment.

Animals↗

PubMed1981

Effects of anorexigenic peptide on gastric and pancreatic secretion.

1. Gastric and pancreatic secretion as well as serum gastrin an insulin levels have been measured after sham-feeding, real feeding or exogenous hormonal stimulation in conscious dogs receiving (pyro) Glu-His-Gly, an appetite depressing peptide (AP). 2. Sham-feeding produced a marked increase in gastric acid and pepsin outputs accompanied by an elevation of serum gastrin and insulin concentrations. AP infusion before and after sham-feeding reduced the peak gastric secretion and suppressed gastrin and insulin responses to sham-feeding. 3. Liver extract meal administered into the stomach resulted in an increase in gastric acid and serum gastrin and insulin levels. AP inhibited acid response to liver extract without affecting serum hormonal levels. Pentagastrin stimulation produced similar acid secretion to that obtained with liver extract and AP infusion also inhibited this secretion. 4. Secretin infusion or feeding a meat meal produced a similar rate of pancreatic bicarbonate secretion in dogs with chronic pancreatic fistula. AP infusion inhibited the bicarbonate response to feeding or secretin without affecting serum gastrin or insulin levels. 5. This study demonstrates that pyro-Glo-His-Gly suppresses serum hormonal and gastric secretory response to cephalic stimulation and reduces gastrin and pancreatic secretory responses to ordinary feeding or exogenous hormonal stimuli.

Animals↗

PubMed1981

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 (0.25-2.0 nmol.kg-1.h-1) caused a slight but significant increase in pancreatic secretions in fasted dogs, but, when given during the secretory stimulation, they caused significant inhibition of these secretions. They reduced gastric acid response to pentagastrin and peptone meal without affecting the serum gastrin level. They caused dose-dependent inhibition of secretin-induced pancreatic bicarbonate secretion and suppressed the pancreatic protein response to caerulein, feeding, and duodenal acidification. SP6-11 was equipotent on a molar basis with SP in the inhibition of gastric or pancreatic secretion, indicating that the C-terminal portion of SP exhibits a full spectrum of the biological action of the intact molecule. The inhibitory effects of SP and SP6-11 on the stomach and pancreas were observed at a dose range that was without any significant influence on the blood pressure, indicating that they are not caused by the interference of the blood flow to the pancreas.

Animals↗

PubMed1981

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. The inhibition of pancreatic secretion by luminal somatostatin was accompanied by a significant increase of plasma levels of the immunoreactive somatostatin, indicating that this peptide can be absorbed intact across the intestinal mucosa. We conclude that somatostatin administered into the gut lumen is absorbed into the circulation and can inhibit pancreatic secretion both by the suppression of the release of gastrointestinal hormones and by direct inhibitory action on the exocrine pancreas.

Animals↗

PubMed1981

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. The peak pancreatic protein, but not bicarbonate response to sham-feeding was reduced by about 31% by BPP. This reduction by BPP amounted to about 57% when the pancreas was stimulated maximally by OP-CCK. It is concluded the PP released by cephalic-vagal excitation does not affect gastric secretion, but inhibits pancreatic protein secretion, and thus might contribute to the lower pancreatic response to sham-feeding as compared with that produced by exogenous stimulants such as secretin and OP-CCK.

Animals↗

PubMed1980

Enkephalin inhibits the release and action of secretin on pancreatic secretion in the dog.

1. Pancreatic bicarbonate and protein secretion as well as immuno-reactive plasma secretin concentration in response to a meal, duodenal acidification and exogenous secretin or octapeptide of cholecystokinin (OP-CCK) have been measured following administration of methionine-enkephalin in chronic pancreatic fistula dogs. 2. Methionine-enkephalin inhibited pancreatic responses to both exogenous hormones (secretin and OP-CCK) and to endogenous hormones released from the gut by food or duodenal acidification. 3. Naloxone, a potent opiate receptor antagonist, partly prevents this methionine-enkephalin-induced inhibition of pancreatic secretion suggesting that this effect might be mediated by opiate receptors. 4. The inhibitory effect of methionine-enkephalin on pancreatic response to endogenous stimulants was more pronounced than that to exogenous hormones and was accompanied by a significant reduction in plasma immuno-reactive secretin concentration. 5. This study indicates that methionine-enkephalin inhibits pancreatic secretion, at least in part, by suppressing the release of the intestinal hormones stimulating the exocrine pancreas.

Animals↗

PubMed1980

Prostacyclin inhibits pancreatic secretion.

Prostacyclin (PGI2), the major product of arachidonate metabolism in the gastrointestinal tract, was shown to affect gastric blood flow and gastric secretion, but it is unknown whether it also affects pancreatic secretion. This study was designed to determine the influence of PGI2 on pancreatic secretion under basal conditions and in response to exogenous and endogenous stimulants. PGI2 alone given in graded intravenous doses caused a slight pancreatic bicarbonate and protein secretion in fasted dogs. When given during stimulated pancreatic secretion, PGI2 caused a potent inhibition of the bicarbonate and protein secretion induced by feeding a liver meal, by duodenal perfusion with hydrochloric acid or amino acid mixture, and by intravenous infusion of secretin or caerulein. The kinetic analysis showed that the interaction between PGI2 and secretin affecting bicarbonate secretion is of a mixed type (increased half-maximal dose response, decreased calculated maximal response). This indicates that PGI2 decreases both the total secretory capacity of the pancreas to secrete bicarbonate and reduces the sensitivity of the pancreatic secretory cells to secretin. Because PGI2 significantly reduced the arterial blood pressure, its inhibitory effects on pancreatic secretion could be due, at least in part, to the interference of the blood flow to the pancreas.

Amylases↗

PubMed1980

Comparison of methionine-enkephalin and morphine in the stimulation of gastric acid secretion in the dog.

In dogs with Heidenhain pouches and gastric fistulas, we studied acid secretion in response to systemic or portal infusion of methionine-enkephalin (met-enkephalin), enkephalin-analog, or morphine. All these opiate compounds caused a dose-dependent increase in acid secretion under basal conditions and resulted in a significant rise in pentagastrin- or histamine-induced acid secretion. The stimulation by opiates of gastric secretion was accompanied by an increase in the mucosal blood flow but without any significant change in serum gastrin concentration. Gastric acid stimulation by met-enkephalin and morphine was strongly inhibited not only by naloxone, an opiate antagonist, but also by blockers of H2-receptors (metiamide) or cholinergic receptors (atropine), suggesting a cooperative interaction between opiates and other stimuli of parietal cells. The gastric stimulation by met-enkephalin and its analog, but not by morphine, was markedly reduced by portal administration of these compounds, indicating a marked inactivation of opiate peptides by hepatic transit. This study shows that enkephalin and morphine stimulate gastric acid secretion by a gastrin-independent mechanism sensitive to atropine and H2-blocker and probably involving opiate receptors.

Animals↗