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Biomedical subjects

S Domschke

Publications and source records attributed to S Domschke.

At least 73 records · Page 4Linked to original sources

Effect of low dose secretin and caerulein on pure pancreatic bicarbonate secretion and plasma secretin in man.

In six healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the main pancreatic duct. Following a 20-min basal period, secretin (0.03 CU/kg, h) was intravenously infused alone for 20 min and then with caerulein 15 ng/kg, h for further 20 min. From a basal level of 28 +/- 13 mu mol/5 min, secretin by itself significantly increased pancreatic bicarbonate to 182 +/- 24 mu mol/5 min. A further significant two-fold increase to 396 +/- 50 mu mol/5 min was observed during caerulein. The increment in plasma secretin of 2.1 +/- 0.3 pmol/l is comparable to the rise that may be observed post-prandially. It is concluded that secretin in combination with cholecystokinin may indeed play a physiological role in the regulation of duodenal pH.

Adult↗

Histamine-release in rat gastric mucosa by pentagastrin.

The release of histamine from isolated gastric mucosa of the rat was studied by a superfusion model. Pentagastrin increased the basal efflux of histamine in a dose dependent manner. Secretin failed to influence the release of histamine under similar conditions. The results are compatible with the view that in gastric mucosa pentagastrin releases histamine which then may react with the receptors of the parietal cell thus serving as mediator in the acid secretory process.

Animals↗

Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects.

Graded doses of 0.6, 1.3, and 3.3 pmol/kg/min of vasoactive intestinal peptide (VIP) were intravenously infused over 30 minute periods in four healthy volunteers and plasma VIP levels were measured by radioimmunoassay. Even with the smallest dose of VIP, plasma concentrations rose markedly above normal values. Infusion of higher VIP doses resulted in mean plateau levels of circulating VIP which were in the range of VIP values found in the Verner-Morrison syndrome. After cessation of the VIP infusions, plasma VIP levels fell strikingly by first order kinetics with an average disappearance half-time of one minute. The apparent metabolic clearance rate was about 9 ml/kg/min and the apparent volume of distribution for VIP was approximately 14 ml/kg. During infusion of the highest VIP dose, previously shown to induce one-fifth maximum pancreatic juice secretion, plasma concentrations of glucose, free fatty acids, and calcium were slightly but significantly raised, the pulse rate and the amplitude of blood pressure were increased, and cutaneous flushing occurred. The spectrum of effects accords well with some abnormalities seen in the Verner-Morrison syndrome. The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions.

Adult↗

Prostaglandin-stimulated gastric mucus secretion in man.

In 6 healthy volunteers, following intragastric instillation of a prostaglandin analogue pentagastrinstimulated gastric secretion of acid, pepsin, and glycoprotein N-acetylneuraminic acid (NANA) was assessed. There was only a slight and statistically insignificant inhibition of acid output while pepsin secretion remained entirely unaffected. On the other hand, gastric mucus (NANA) secretion was significantly increased dependent on the prostaglandin dose administered. It is concluded that prostaglandins in addition to their well-known gastric acid inhibitory action may exert mucus stimulating properties and thus may have a direct protective effect on the gastric mucosa.

Adult↗

Effects of vasoactive intestinal peptide on resting and pentagastrin-stimulated lower esophageal sphincter pressure.

Vasoactive intestinal peptide (VIP) administered as an intravenous infusion at different doses (0.8, 1.6, and 3.2 micrograms per kg per hr, respectively) inhibited dose-dependently the response of the lower esophageal sphincter to an intravenous injection of pentagastrin (0.6 microgram per kg) in 4 healthy volunteers. Inhibition ranged from about 20% (not significant) with the low dose to about 55% (P less than 0.05) with the high dose. On the other hand, the VIP doses employed did not substantially decrease basal lower esophageal sphincter pressure. Calculated on the basis of plasma levels of the respective peptides, the inhibitory effect of VIP was about one-third of that of secretin. Even at the smallest dose of VIP, plasma levels of radioimmunoassayable VIP (20 to 100 pmoles per liter) markedly exceeded those encountered normally (1 to 19 pmoles per liter). So, the data presented do not support the suggestion that normally circulating VIP essentially contributes to the physiological regulation of the lower esophageal sphincter pressure; they do not exclude, however, such a role for locally released VIP.

Adult↗

Release of VIP, secretin and motilin after duodenal acidification in man.

Plasma VIP, secretin and motilin were measured in 9 volunteers following intraduodenal instillation of 50 ml of 0.1 mol/1 HCl over 3 minutes. VIP rose from 1.7 +/- 0.7 pmol/1 to a peak at 6 minutes of 6.6 +/- 0.9 pmol/1 and was still significantly elevated at 30 minutes. By comparison the elevation of secretin was more transitory rising from a basal value of 2.5 +/- 0.4 pmol/1 to a peak of 10 +/- 1.5 pmol/1 at 3 minutes and returning to baseline by 10 minutes. The rise of motilin, from a higher baseline, was intermediate in pattern, from 23 +/- 7 pmol/1 basally to a 4 minute peak of 40 +/- 10 pmol/1. Thus the elevation of VIP was the most longlasting, and while probably not of sufficient magnitude to stimulate pancreatic bicarbonate secretion via the circulation, could reflect a significant local role in regulating the response of the intestinal mucosa to acid.

Bicarbonates↗

[Treatment of peptic ulcer with histamine H2 receptor antagonists].

Histamine H2-receptor antagonists (Burimamide, Metiamide and Cimetidine as the most recent generation) may drastically inhibit gastric acid secretion stimulated by histamine, pentagastrin, insulin, 2-deoxyglucose or an intragastrically instilled meal, respectively. This inhibitory action may explain the beneficial effects of H2-antagonists in the treatment of active peptic ulceration. On Cimetidine administered at a usual dosage over a 4--6 week period, serious side-effects must not be expected. At present studies aim to establish a Cimetidine dosage which, on long-term treatment, may reduce ulcer recurrency.

Burimamide↗

Secretin-induced histamine release in duodenal-ulcer patients.

Because a majority of duodenal-ulcer patients responded locally to intradermal secretin, skin samples from 7 patients with duodenal ulceration and 6 patients with goitre or cholelithiasis were incubated with "tris" buffer alone and with tris buffer containing 20 C.U./ml synthetic secretin or 100 microng/ml compound 48/80. Skin from duodenal-ulcer patients released significantly more histamine than did that of controls (p less 0-01). Histological examination of skin samples from these patients showed that the number of histamine-containing mast-cells averaged 5-7 per field and dropped to 1-2 per field after incubation with secretin. It is concluded that in a certain type of duodenal ulceration intradermal secretin releases histamine from mast-cells and thus induces a local anaphylactic reaction. This might prove suitable for preclinical ulcer diagnosis and/or for detection of patients at risk of acquiring that disease.

Adult↗

[New views on gastrointestinal hormones].

In addition to established gastrointestinal hormones--secretin, cholecystokinin-pancreozymin (CCK-PZ), gastrin, and glucagon---some 30 polypeptides with gastrointestinal actions can be listed. New aspects of these substances include the following: Gastrin and vasoactive intestinal peptide (VIP) can be also encountered in the central nervous system and may act as transmitters. CCK-PZ-serum concentrations are found markedly elevated in patients with exocrine pancreatic insufficiency; this may provide the opportunity to establish a realtively simple screening test. Moreover, there is evidence that serum-CCK-PZ levels serve as satiety signal. Secretin secretion is said to be enhanced in hunger and then to act as a lipolytic hormone. In addition to enteroglucagon, a gastrintestinal peptide identical to pancreatic glucagon has been detected. Gastric inhibitory polypeptide (GIP) inhibits gastric secretion and motility (enterogastrone activity) and together with glucose it stimulates insulin release (incretin activity). Motilin increases lower esophageal sphincter pressure, enhances gastric pepsin secretion and slows down gastric evacuation. Serum levels of pancreatic polypeptide may be found elevated as a diagnostic index in patients with endocrine peptide tumors of the pancreas. Recently, the potential importance of local (paracrine) actions of gastrointestinal polypeptides has been amphasized. Predominantly paracrine activity is exhibited by some prototype hormones, e.g. somatostatin, substance P, bombesian, and the non-polypeptide compounds, prostaglandins.

Bombesin↗

Influence of enkephalin on K+-evoked efflux of putative neurotransmitters in rat brain. Selective inhibition of acetylcholine and dopamine release.

In rat brain slices preincubated with various radiolabelled putative neurotransmitters, methionine-enkephalin diminished the potassium-evoked release of dopamine and acetylcholine. The effect was antagonised by naloxone. The potassium-induced effux of three other neurotransmitters, histamine, 5-hydroxy-tryptamine and gamma-aminobutyric acid, were unaffected by methionine-enkephalin. A probable physiological function for the endogenous ligands in specifically affecting the catecholaminergic and cholinergic transmission is suggested.

Acetylcholine↗

Gastric epithelial cell turnover, mucus production, and healing of gastric ulcers with carbenoxolone.

Nineteen healthy subjects were studied and 17 patients with gastric ulcer before and after ulcer healing with carbenoxolone. Gastric deoxytibonucleic acid (DNA) loss was measured as an index of epithelial cell turnover, and N-acetylneuraminic acid (NANA) content of gastric juice as an index of mucus secretion. In normal subjects there was a negative correlation (p less that 0-025) between gastric DNA loss and NANA secretion; the lower the cell turnover the higher the NANA production. In gastric ulcer patients DNA loss or turnover was significantly (p less than 0-01) higher than normal, and fell significantly (p less than 0-01) after four weeks' treatment with carbenoxolone when 16 of the 17 ulcers had healed. At the same time NANA output increased significantly (p less than 0-01). It is suggested that patients with gastric ulcer lose cells at a high rate, a state of affairs which is returned towards normal by carbenoxolone, thus allowing the epithelial cells to mature within the mucosa and produce more mucus.

Adult↗

Plasma secretin and pancreatic bicarbonate response to exogenous secretin in man.

The dose response of duodenal bicarbonate production during synthetic porcine secretin infusions was studied in six healthy volunteers and related to plasma secretin immunoreactivity. Secretin was infused in each individual at four different doses from 0-1 to 2-7 CU/kg/h, each infusion lasting for 60 minutes. Mean maximal bicarbonate secretion was 33 +/- 4 mEq/h. The secretin plasma level for half maximal bicarbonate response was estimated to be 22 pmol/l. As this level is reported to be achieved by intraduodenal acidification in man, it is concluded that secretin may well play a part in the control of duodenal pH.

Adult↗

Effect of secretin on plasma motilin in man.

Graded doses of 0-1, 0-3, 0-9, and 2-7 clinical units/kg/h of pure synthetic secretin were infused over 60 minute periods in six healthy volunteers. Duodenal bicarbonate output and pH were recorded and plasma secretin and motilin levels were measured by radioimmunoassay. During the infusions plasma motilin fell in a dose dependent manner to a nadir of 35%. This fall was linearly correlated with pancreatic bicarbonate output, whereas a non-linear correlation was observed between plasma motilin and both plasma secretin level and duodenal pH. It is suggested that plasma motilin levels are decreased by secretin-induced pancreatic bicarbonate juice flow. This may be important for the control of motilin secretion initiated by duodenal acidification and the concomitant delay in gastric emptying.

Adult↗

Comparison of pancreatic responses to portal and systemic secretin and VIP in cats.

This study was designed to compare pancreatic bicarbonate responses to secretin and vasoactive intestinal peptide (VIP) administered either by peripheral or portal route in 24 anesthetized cats. Continuous intravenous infusion of graded doses of secretin (rang from 0.04 to 0.68 nmol/kg per h), stimulated pancreatic volume flow and bicarbonate outputs dose dependently and not statistically differently when given into the peripheral or portal vein. VIP infused in graded doses (range from 0.60 to 9.62 nmol/kg per h) into the peripheral vein produced pancreatic volume flow and bicarbonate outputs not statistically different from those obtained with secretin. In contrast, the biological activity of VIP administered intraportally was reduced by 60% at lower VIP doses (0.60 and 1.20 nmol/kg per h) and by 40% at 2.40 nmol/kg per h, whereas at higher doses it was not significantly changed. This study provides evidence that VIP in the cat is a secretin-like full agonist of pancreatic bicarbonate secretion and that it is only partially inactivated by the liver.

Animals↗

Inhibition by somatostatin of gastrin release and gastric acid responses to meals and to pentagastrin in man.

The inhibitory actions of intravenous somatostatin on the gastric secretory responses to pentagastrin (1.5 microng/kg-h i.v.) and to a meal (10% peptone, pH 5.5) were studied in six healthy subjects. Meal-induced gastric acid output was estimated by means of a modified Fordtran and Walsh method of intragastric titration. Somatostatin (5 microng/kg-h; cyclic form) significantly inhibited the total 1-hour acid response to pentagastrin by about 70% (inhibition of pepsin secretion: about 70%) and that to a test meal by about 75%. During the last 30 min of somatostatin infusion the pentagastrin-stimulated secretion of acid was significantly reduced by about 90% (inhibition of pepsin output: about 85%) while the corresponding figure in the test with meal-induced secretion was about 95%. Serum gastric--elevated in response to the test meal--was found to be merely lowered by about 30% during somatostatin infusion. Consequently, it is tempting to assume that inhibition of human gastric acid secretion by exogenous somatostatin largely results from a direct antisecretory effect upon parietal cells and, only to a minor extent, from an indirect action via reduction of gastrin release.

Adult↗

Inhibition by somatostatin of secretin-stimulated pancreatic secretion in man: a study with pure pancreatic juice.

The action of somatostatin on compostition and flow rate of pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct was evaluated in 5 healthy volunteers. Synthetic secretin (0.06 CU/kg-h) was intravenously infused throughout the 80-min study. Bicarbonate concentrations in pancreatic juice achieved constant levels (117 +/- 3 muEq/ml) after 10 min, whereas a steady state of juice flow (7.3 +/- 1.4 ml/5 min) was attained after 15 min of secretin infusion. In the third 20-min period, cyclic somatostatic (5 mug/kg-h i.v.) was given, leading to a decrease in pancreatic flow rate by 47% after 10 min, and by 67% after 15 min of somatostatin administration. Alrady 5 min after the infusion of somatostatin had been discontinued, pancreatic flow rate gradually recovered; presomatostatin levels, however, were not reached within 20 min. Cyclic AMP varied roughly in accordance with bicarbonate concentrations, whereas the chloride concentrations were reciprocally related. Bicarbonate, sodium, potassium, protein, and cyclic GMP concentrations did not change substantially due to somatostatin.

Adult↗