Measurement of gut hormonal peptides in biopsies from human stomach and proximal small intestine.

Using sensitive and specific radioimmunoassays, concentrations of hormonal peptides have been measured in small biopsies taken from the human stomach, duodenum, and proximal jejunum. Comparison is made of these hormone concentrations and the number of respective endocrine cells present determined by quantitative immunocytochemistry. Immunoreactive somatostatin, VIP, motilin, and gastrin were detected in all regions examined, whereas secretin and GIP were undetectable in antral extracts. Enteroglucagon-like immunoreactivity was present only at and beyond the ligament of Treitz, although a few enteroglucagon-producing cells were shown by immunocytochemistry in the duodenum. The variation of hormone concentration was found to be small in these biopsies of normal tissue within each region of the gut examined, indicating that representative hormone concentrations may be reliably obtained from small biopsy tissues. An attempt has been made to establish reference values for gut hormone concentrations in such biopsies; this may allow future study of any changes in concentration that may occur in pathological conditions.

Influence of ethanol on histamine metabolism and release in the rat brain. II. Regions of the histaminergic pathway.

Following acute alcohol administration (80-160 mg/100 g body weight) histamine levels of rat brain cortex and thalamus were elevated and histidine decarboxylase activity was decreased. The effect was less pronounced after chronic alcohol treatment (15% v/v in drinking water for 4 weeks). In the striatum there was no change in the metabolic pattern of histamine. Histamine-N-methyltransferase was unaffected in either case. Depolarisation-induced release of histamine was inhibited by alcohol in the hypothalamus, thalamus and cortex. The results indicate that ethanol affects the histamine metabolism and release processes in the histaminergic pathway of the brain.

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.

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.

[Drug interactions in the intestinal tract]. / Arzneimittel-Interaktionen im Intestinaltrakt.

The mechanisms of drug-drug interactions are generally classified and interferences within the gastrointestinal tract are discussed. The latter mainly concern interactions in which absorption of a drug is affected. Unwanted reactions may easily be avoided by choosing carefully combination and time of administration of two or more drugs to be used in a patient.

[The influence of ether anesthesia in white mice on the contents of cyclic nucleotides in their brain and of cyclic nucleotides and glycogen in their liver (author's transl)]. / Der Einfluss einer Athernarkose auf den Gehalt des Gehirns weisser Mäuse an zyklischen Nukleotiden und der Leber an zyklischen Nukleotiden und Glykogen.

During ether narcosis (10% diethyl ether v/v) of 30 min in white mice, the brain content of cAMP and cGMP is significantly diminished. By contrast, the liver cAMP and cGMP concentrations are increased 5 and 30 min after beginning narcosis but there is no or little difference, respectively, as compared to controls after 60 min. Liver glycogen content is elevated after 5 min but is diminished after 30 and 60 min as compared to controls. Pretreatment of the animals with the alpha-blocking agent phentolamine and the beta-blocking agent propranolol, respectively, prevents neither the increase in liver cAMP nor the decrease in liver glycogen during ether narcosis. It may be assumed that the changes in the liver and brain contents of cAMP and cGMP during ether application are due to physico-chemical alterations at the cell membrane which result in changes of the activity of the enzymes adenylate cyclase and guanylate cyclase in brain and liver tissue.

A rapid and sensitive enzymatic-isotopic method for routine assay of histamine in blood, plasma and biopsy tissue: re-evaluation.

The enzymatic-isotopic method for determination of histamine has been reevaluated. Modifications, permitting routine analysis of the amine in blood, plasma and biopsy tissues of various origin have been described; this permits convenient application of the technique in various fields of clinical pharmacology, gastroenterology and immunology.

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.

Regional levels of histamine in rat brain after microwave irradiation: evidence for artifacts in the enzymatic--isotopic assay.

Histamine levels in the brain, measured fluorimetrically, were similar for rats killed by decapitation and microwave irradiation. However, enzymatic--isotopic assay yields 5--20 times higher value for microwave irradiation versus decapitation. Thin layer chromatography of the methylated products in the enzymatic--isotopic assay indicated the formation of artifacts following microwave irradiation. The results strongly suggest that a combination of microwave irradiation and enzymatic--isotopic assay is not suitable for histamine analysis in the rat brain.

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.

[Radioimmunoassay of motilin (author's transl)]. / Die radioimmunologische Bestimmung von Motilin.

A specific radioimmunoassay for motilin is described and a few technical details concerning antibody production and tracer iodination are discussed. Though a variety of biological actions of motilin have been reported, its role in normal human physiology remains to be established. So far, the motilin radioimmunoassay brought no major break through to elucidate the physiology, disregard pathophysiology, of motilin.

Motilin release in the pig.

Motilin is found in the upper intestine of pig and man and in man is released by acid. A similar release by acid has now been found in the pig and is associated with markedly reduced immunostainable motilin in the upper small intestine. Clamping the arteries and veins to the stimulated segment immediately reversed the rise of plasma motilin, indicating the motilin release to be an entirely local phenomenon. The apparent half life of endogenous motilin was 3.9 minutes. No release of motilin was seen after a meal and the possible physiological role of motilin thus remains speculative.

Ethanol-induced alterations in histamine content and release in the rat hypothalamus.

In the rat hypothalamus, histamine content and histidine decarboxylas: activity are enhanced significantly after acute administration (80--160 mg/100g body weight) of ethanol. The effects are less pronounced after chronic treatment (15% v/v in drinking water for 4 weeks). Histamine methyltransferase is unaffected in either case. In hypothalamic slices preloaded with 3H-histamine and superfused with amine free solution the basal and K+-induced efflux of 3H-histamine are inhibited by alcohol. The inhibition of histamine release along with the increased levels of histamine may play an important role in the central effects of alcohol.

Lysine acetylisalicylate inhibits the protein synthesis in the rat gastric mucosa in vivo and in vitro.

Lysine acetylsalicylate (LAS), a water soluble derivative of acetylsalicylic acid and parenterally administrable analgesic, locally inhibits the incorporation of 14C protein hydrolysate into proteins of the rat isolated gastric mucosa. A similar effect on protein synthesis was observed after s.c. administration of the drug, whereas DNA and RNA synthesis were not affected. Obviously, LAS inhibits the translation step during biosynthesis of proteins. It is conceivable that this effect contributes to the potential ulcerogenic action of acetylsalicylate and that parenteral administration is not a criteria to protect the stomach from salicylate-induced side effects.