Metabolism of two adrenocorticotrophin analogues in the intestine of the rat

1. At 30min after oral administration unchanged Synacthen [corticotrophin-(1–24)-tetracosapeptide] was found in the stomach but could not be detected in the lumen of the small intestine of the rat. 2. Synacthen and 41795-Ba {[d-Ser1, Lys17, Lys18]corticotrophin-(1–18)-octadecapeptide amide} were rapidly metabolized in vitro by both intestinal juice and everted pieces of small intestine. Peptide products were not found either in the intestinal tissue or in the fluid bathing the serosal tissue. 3. Glucose but not O2 was necessary for the breakdown of the two adrenocorticotrophin analogues by everted tissue. 4. When the products obtained after partial digestion were chromatographically separated and identified, a pattern of breakdown emerged. The N-terminus of Synacthen and the Phe(7)–Arg(8) bond in both analogues were particularly labile. The d-serine N-terminal residue of 41795-Ba conferred a marked protection to aminopeptidase action. 5. The relative susceptibilities of peptide bonds would have been difficult to predict on the basis of existing knowledge of the properties of enzymes of the small intestine.

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Differences in uptake and esterification of saturated analogues of cholesterol by rat small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.251.4.g495 ◽

1986 ◽

Vol 251 (4) ◽

pp. G495-G500 ◽

Cited By ~ 2

Author(s):

A. K. Bhattacharyya

Keyword(s):

Small Intestine ◽

Intestinal Mucosa ◽

Cholesterol Content ◽

Cell Uptake ◽

Cholesterol Concentration ◽

Mucosal Cell ◽

Rat Small Intestine ◽

Intestinal Tissue

Coprostanol and cholestanol are two saturated analogues of cholesterol. The former, which is the A/B ring isomer of cholesterol, is a nonabsorbable sterol, whereas the latter, which has an A/B ring configuration closer to that of cholesterol, is absorbed only half as efficiently as cholesterol. Intestinal mucosal cell uptake and esterification, two important steps in absorption, were studied in vivo after feeding the sterols and in vitro using everted sacs of rat small intestine. The results showed that the intestinal tissue content of coprostanol, total and esterified, were significantly lower than that of cholestanol. Total cholesterol concentration in the intestinal tissue was similar throughout but the esterified cholesterol content increased significantly throughout the length of the intestine compared with controls. The study suggests that cholestanol is absorbable because its uptake and esterification are not limited, whereas coprostanol is nonabsorbable because its uptake and esterification are limited in the intestinal mucosa. Also, the two sterols stimulate the activities of cholesterol esterase, one of the cholesterol esterifying enzymes, in the intestinal mucosa. The present study along with previous studies suggests that the structure of the sterol molecule as a whole appears to be the important determinant for its uptake and esterification, and probably absorption, in the small intestine.

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COMPARISON OF THE METABOLISM OF TESTOSTERONE UNDECANOATE AND TESTOSTERONE IN THE GASTROINTESTINAL WALL OF THE RAT IN VITRO AND IN VIVO

Acta Endocrinologica ◽

10.1530/acta.0.0860216 ◽

1977 ◽

Vol 86 (1) ◽

pp. 216-224 ◽

Cited By ~ 7

Author(s):

J. Geelen ◽

A. Coert ◽

R. Meijer ◽

J. van der Vies

Keyword(s):

Small Intestine ◽

Gastrointestinal Tract ◽

Portal Vein ◽

Oral Administration ◽

Small Extent ◽

Great Similarity ◽

Testosterone Undecanoate ◽

Different Parts

ABSTRACT The metabolism of testosterone undecanoate (TU) and testosterone (T) is studied in the gastrointestinal wall of the rat in vitro. A comparison is made with the in vivo metabolism of these compounds in the rat. The major metabolite first appearing during incubation of TU with the small intestine is T. Incubation of TU or T with the small intestine reveals a great similarity between the metabolite patterns obtained. This is also the case with the patterns derived from portal vein plasma upon oral administration of TU and T. Incubation of different parts of the gastrointestinal tract with TU or T shows that the greatest metabolic activity is located in the wall of the small intestine. Unlike T, TU is metabolized only to a small extent in the wall of the stomach and the large intestine.

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Specificity studies on enteropeptidase substrates related to the N-terminus of trypsinogen

Biochemical Journal ◽

10.1042/bj2410721 ◽

1987 ◽

Vol 241 (3) ◽

pp. 721-727 ◽

Cited By ~ 3

Author(s):

P Jenö ◽

J R Green ◽

M J Lentze

Keyword(s):

Small Intestine ◽

Methyl Ester ◽

Rat Small Intestine ◽

Concerted Action ◽

Intestinal Tissue ◽

Alternative Substrates ◽

Synthetic Substrate ◽

Highly Active ◽

N Terminus ◽

Aminopeptidase A

The specificity of the synthetic substrate Gly-[L-Asp]4-L-Lys 2-naphthylamide originally developed for the assay of enteropeptidase (EC 3.4.21.9), was investigated with partially purified aminopeptidase. Our results indicate that, not only enteropeptidase, but also the concerted action of the aminopeptidases of the rat small intestine, can rapidly release 2-naphthylamine from the substrate. A previously undescribed, highly active, dipeptidylaminopeptidase, which hydrolyses a Gly-Asp dipeptide from the N-terminus of the substrate, was detected in rat small intestine. The resulting [L-Asp]3-L-Lys 2-naphthylamide fragment is then degraded by a combination of aminopeptidase A and N to yield free 2-naphthylamine. Thus the present substrate cannot be regarded as being specific for enteropeptidase, and its use leads to an over-estimation of enteropeptidase activity in homogenates and extracts of intestinal tissue. In order to prevent this non-specific hydrolysis by aminopeptidases, stereoisomeric substrates with the sequence L-Ala-D-Asp-[L-Asp]3-L-Lys methyl ester, D-Ala-[L-Asp]4-L-Lys methyl ester and L-Ala-[Asp]4-L-Lys methyl ester were synthesized and tested as alternative substrates by their ability to inhibit the enteropeptidase-catalysed activation of trypsinogen.

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In Vitro Absorption of Radioiron by Everted Pouches of Rat Intestine

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.194.2.319 ◽

1958 ◽

Vol 194 (2) ◽

pp. 319-326 ◽

Cited By ~ 47

Author(s):

Elmer B. Brown ◽

Bertram W. Justus

Keyword(s):

Small Intestine ◽

Ferrous Iron ◽

Ferric Iron ◽

Metabolic Inhibitors ◽

Passive Transport ◽

Rat Intestine ◽

Intestinal Tissue

Everted pouches of rat intestine prepared by the technique of Wilson and associates were used to measure absorption of radioiron. Iron was taken up equally well in vitro by all segments of the rat's small intestine; but when the iron was given orally in vivo, a distinct gradient, highest in the duodenum and progressively smaller in the distal segments was demonstrated. There was little transfer into the inner serosal pouch. Transfer of iron in this preparation was by a process of passive transport. It was not appreciably affected by changes in pH, various metabolic inhibitors, buffer systems, or added substrates. Ferrous iron was significantly better taken up by the intestinal tissue, but transfer into the inner pouch fluid was greater with ferric iron.

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Effects of Nondigestible Oligosaccharides onSalmonella enterica Serovar Typhimurium and NonpathogenicEscherichia coli in the Pig Small Intestine In Vitro

Applied and Environmental Microbiology ◽

10.1128/aem.67.8.3391-3395.2001 ◽

2001 ◽

Vol 67 (8) ◽

pp. 3391-3395 ◽

Cited By ~ 45

Author(s):

Patrick J. Naughton ◽

Lene Lind Mikkelsen ◽

Bent Borg Jensen

Keyword(s):

Small Intestine ◽

Standard Diet ◽

Organ Cultures ◽

Intestinal Tissue ◽

Tissue Model ◽

E Coli ◽

Serovar Typhimurium ◽

Ileal Tissue ◽

Bacterial Association

ABSTRACT An in vitro intestinal tissue model was developed for the investigation of bacterial association in the pig small intestine under different dietary regimes. In preliminary experiments, jejunal and ileal tissue was taken from Danish Landrace pigs fed standard diet and inoculated with either Salmonella or nonpathogenicEscherichia coli strains. Higher numbers of salmonellae associated with the ileal tissues, but the numbers did not reach significance. Hence, jejunal sections were inoculated with nonpathogenic E. coli and ileal sections were inoculated with salmonellae in the presence of mannose or commercial nondigestible oligosaccharides (NDO) at 2.5%. There was a significant decrease inE. coli associated with the jejunum in the presence of mannose (P < 0.05). Furthermore, in pigs fed a diet supplemented with commercial NDO at 4% there was a significant reduction in the numbers of E. coli in jejunal organ cultures of pigs fed the FOS diet (P < 0.05). There was a reduction, though not a significant one, in the association ofSalmonella sp. to the ileal sections of pigs fed the commercial FOS diet. The feeding of commercial GOS or its addition to organ cultures did not affect E. coli orSalmonella numbers.

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INHIBITION OF THEILER'S ENCEPHALOMYELITIS VIRUS (GDVII STRAIN) OF MICE BY AN INTESTINAL MUCOPOLYSACCHARIDE

Journal of Experimental Medicine ◽

10.1084/jem.98.5.399 ◽

1953 ◽

Vol 98 (5) ◽

pp. 399-415 ◽

Cited By ~ 18

Author(s):

Benjamin Mandel ◽

Efraim Racker

Keyword(s):

Small Intestine ◽

Adult Mouse ◽

Reducing Sugars ◽

Theiler's Virus ◽

Intestinal Tissue ◽

Adult Mice ◽

Encephalomyelitis Virus ◽

Mouse Intestine

A mucopolysaccharide has been obtained from intestinal tissue of adult mice which inhibits both infectivity and hemagglutination of Theiler's GDVII strain of encephalomyelitis virus of mice. The inhibitor is inactive against the FA and TO strains of Theiler's virus and against the Lansing strain of poliomyelitis virus. In the adult mouse, large amounts of the inhibitor are found only in the small intestine. The small intestine of infant mice, however, contains a considerably smaller amount of inhibitor. Inhibition, both in vivo and in vitro, appears to be the result of an interaction between virus and inhibitor. The intestines of man, monkey, rabbit, rat, cotton rat, hamster, sheep, cow, and pig contain relatively little inhibitor whereas guinea pig intestine contains as much as adult mouse intestine. An enzyme was found in the feces of mice, and several other animals, which is capable of destroying the inhibitory activity of the mucopolysaccharide with the liberation of reducing sugars.

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Reserve capacities of the small intestine for absorption of energy

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.1.r300 ◽

1998 ◽

Vol 275 (1) ◽

pp. R300-R307 ◽

Cited By ~ 1

Author(s):

E. Weber ◽

H. J. Ehrlein

Keyword(s):

Small Intestine ◽

Gastric Emptying ◽

Oral Administration ◽

Nutrient Composition ◽

Reserve Capacity ◽

Intestinal Length ◽

Saturation Kinetics ◽

Complete Absorption ◽

Nutrient Solutions

Previous in vitro studies showed that the small intestine has reserve capacities for absorption of nutrients. However, the size of the reserve capacity is controversial. Therefore, we measured the intestinal capacity for absorption of energy in relation to the postprandial gastric delivery of energy into the gut. In minipigs, a 150-cm length of jejunum was perfused (1–8 kcal/min) with four nutrient solutions containing 60% of energy as carbohydrate, protein, and fat, respectively, or containing 33.3% of each nutrient. In separate experiments, gastric delivery of energy to the jejunum was measured after oral administration of four meals with the same nutrient composition as the perfusion solutions. With all nutrient solutions, intestinal absorption of energy demonstrated saturation kinetics. The jejunal capacity for absorption of energy ranged from 0.66 to 0.94 kcal ⋅ m−1 ⋅ min−1. Despite large differences in nutrient composition of the four meals, equal amounts of energy (1.3 ± 0.41 kcal/min) were delivered from the stomach to the jejunum. The absorption rates of energy after meals ranged from 0.40 to 0.58 kcal ⋅ m−1 ⋅ min−1. Therefore, only 58.8 ± 2.7% of the jejunal capacity for absorption of energy was used. Additionally, the length of small intestine that would have been required for complete absorption was 42.9 ± 3.7% of the total length. Results indicate that the feedback control of gastric emptying provides at least two types of intestinal reserve capacities: a reserve in absorption (1.7 fold) and a reserve in intestinal length (2.4 fold).

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Electron probe x-ray microanalysis and electron microscopy of amino acid absorption and transport by the small intestine: inhibition by chemical poisons and correlation to the elemental composition of the epithelial cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142311 ◽

1986 ◽

Vol 44 ◽

pp. 134-135

Author(s):

A. J. Tousimis

Keyword(s):

Small Intestine ◽

Amino Acid ◽

Epithelial Cells ◽

Elemental Composition ◽

Isotope Labeling ◽

Structural Components ◽

X Ray ◽

Human Small Intestine ◽

Transport Studies

The elemental composition of amino acids is similar to that of the major structural components of the epithelial cells of the small intestine and other tissues. Therefore, their subcellular localization and concentration measurements are not possible by x-ray microanalysis. Radioactive isotope labeling: I131-tyrosine, Se75-methionine and S35-methionine have been successfully employed in numerous absorption and transport studies. The latter two have been utilized both in vitro and vivo, with similar results in the hamster and human small intestine. Non-radioactive Selenomethionine, since its absorption/transport behavior is assumed to be the same as that of Se75- methionine and S75-methionine could serve as a compound tracer for this amino acid.

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