PubMed Health⌕ Search

Biomedical subjects

E Wünsch

Publications and source records attributed to E Wünsch.

At least 91 records · Page 5Linked to original sources

Immunohistochemical localization of motilin in endocrine non-enterochromaffin cells of the small intestine of humans and monkey.

Motilin-immunoreactive cells in the human and monkey duodenum and upper jejunum were investigated by immunofluorescence (IF) and peroxidase-antiperoxidase (PAP) techniques using antibodies against synthetic 13-norleucine motilin and synthetic porcine motilin. Contrary to previous reports, we have demonstrated that motilin-immunoreactive cells are a distinct cell population that does not correspond to 5-hydroxytryptamine-containing enterochromaffin (EC-) cells. EC-cells, indentified by formaldehyde-induced fluorescence (FIF) or by argentaffinity (AA), do not react with either antisera. EC-cells of the monkey, utilizing one method (PAP), reacted to one antiserum very weakly. This reaction was also suppressed by absorption with 13-norleucine motilin. It is suggested that the EC-cells of the monkey contain either a very small amount of motilin or another peptide that exhibits a part of the amino acid sequence of motilin. The discrepancy between these results and those of other authors can be explained by the different reactivity of the antisera used.

Animals↗

Interaction of synthetic human big gastrin with blood proteins of man and animals.

Radio gel and affin chromatography were used to study big gastrin interaction with blood proteins of man and animals. The experiments showed that big gastrin interacts with serum proteins in vitro. The gastrin-blood protein complex is labile and readily dissociates (T 1/2 = 8--14 min). A more stable complex is found in acidic medium. Ceruloplasmin is one of the blood serum proteins able to interact with big gastrin. The stability of hormone-protein complex, formed by gastrin and ceruloplasmin, is dependent upon hormone concentration. With the addition of C-terminal penta--and octapeptides to labelled hormone, binding increased. It is speculated that formation of labile gastrin-blood protein complexes is necessary for selective gastrin transport from hormone-producing cells to target cells.

Animals↗

Quantitative comparison of the effects of cholecystokinin, secretin, and pentagastrin on gastrointestinal myoelectric activity in the conscious fasted dog.

The effects on gastrointestinal myoelectric activity of infused pentagastrin, cholecystokinin (CCK), and secretin at physiological doses were studied in live dogs with implanted serosal electrodes during 56 six-hour studies. Pentagastrin dose-dependently increased gastric and duodenal slow-wave frequencies; secretin and CCK did not. Pentagastrin and CCK diminished the incidence of fasting migrating myoelectric complexes (MMCs), but MMCs were abolished only in the proximal small intestine. Pentagastrin infusion was not reflected in an increased number of spikes, whereas CCK induced a dose-dependent increase in jejunal spike activity. Secretin dose-dependently decreased duodenal and jejunal spike incidence without a marked effect on MMC incidence. Analysis of patterns of spike activity showed significant dose-dependent changes with all three peptides. The different effects of pentagastrin and CCK on spike activity in these studies may have been a consequence of pentagastrin-stimulated gastric acid secretion. None of the three peptides produced a pattern of myoelectric activity which closely resembled that seen on feeding; since, unlike food, all three peptides had little or no effect on the distal small intestine, it seems unlikely that combinations of these peptides are responsible for the change induced by food. The failure of these peptides to abolish fasting patterns in the distal intestine suggests a possible mechanism for some types of post-vagotomy dysfunction.

Action Potentials↗

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↗

[Synthesis of human [11-leucine]minigastrin I--II. Purification of the synthetic tridecapeptide amide and isolation of a side-product (author's transl)].

The preparation of the pure 11-leucine analogue of human minigastrin I, a linear tridecapeptidaemide with full "gastrin activity", from the crude synthetic material obtained after deblocking of the overall protected tridecapeptide amide derivative by means of trifluoroacetic acid, is achieved by ion-exchange chromatography on DEAE-Sephadex A-25 and subsequent partition chromatography on Sephadex G-25. The isolation of a synthetic side-product and its identification as human [10-(Nin-tert-butyl-tryptophan),11-leucine]minigastrin I by means of spectroscopic (UV, fluorescence, 1H-NMR, MS), enzymatic and chromatographic methods is described. The pure tridecapeptide amides human [Leu11]minigastrin I and human [Trp(1'-But)10,Leu11]minigastrin I are isolated in overall yields of 37.4% and 4.6%, respectively (mol-% with regard to the overall protected tridecapeptide amide derivative).

Amides↗

[Side-reactions in peptide synthesis, III. Synthesis and characterization of Nin-tert-butylated tryptophan derivatives (author's transl)].

It was possible to elucidate a side reaction which had long been assumed to occur during the acidolytic cleavage of protecting groups based on a ter-butyl moiety, by synthesizing Nin-tert-butyltryptophan in different ways. It was found to be absolutely identical with a "modified tryptophan" which was isolated after the total synthesis of a gastrin analogue; Nin-tert-butyl-tryptophan peptides are formed as the main products of a tert-butylation reaction, the mechanism of which is not very clear yet. The proof for a Nin-tert-butylation of tryptophan was obtained by spectroscopic methods, in particular mass spectrometry and nuclear magnetic resonance spectroscopy.

Magnetic Resonance Spectroscopy↗

[Side-reactions in peptide synthesis, IV. Charactertzation of C- and C,N-teri-butylated tryptophan derivatives (author's transl)].

Besides Nin-tert-butylated tryptophan derivatives, other tert-butyl-tryptophan analoga are also found as a result of side-reactions accurring during the acidolytic cleavage of protecting groups being based on a tert-butyl moiety. C-mono-substitution could be detected as well as di- and tri-substitution. All these tert-butylated tryptophans could be isolated in a pure form from the tert-butylation mixture either free or as derivatives and could unequivocally be identified in particular by means of mass spectrometry and nuclear magnetic resonance spectroscopy.

Magnetic Resonance Spectroscopy↗

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↗

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↗

Effect of 13-NLE-motilin on gastric secretion, serum gastrin level and mucosal blood flow in dogs.

1. In dogs with gastric fistulas and vagally innervated fundic and antral pouches, 13-norleucine-motilin (13-nle-motilin), a synthetic analogue of motilin, infused intravenously in graded doses produced a dose-dependent increase in gastric acid and pepsin outputs. 2. The motilin-induced stimulation of gastric secretion occurred independently of antral pH and was not accompanied by any alteration in the serum gastrin level suggesting that motilin did not affect the release of gastrin. 3. When infused intravenously in a constant dose against a constant background stimulation with pentagastrin or histamine 13-nle-motilin inhibited both acid and pepsin secretion from the main stomach and fundic pouch. 4. The inhibitory effect of 13-nle-motilin was always associated with a marked reduction in mucosal blood flow but without any change in the ratio of aminopyrine concentration in the gastric juice and blood plasma indicating that this peptide primarily affected gastric secretion but did not limit the gastric mucosal microcirculation.

Animals↗

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↗