Title:
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Absorption of tyrosine containing peptides from the gastrointestinal tract of the rat
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The mechanisms of Absorption of Tyrosine containing Peptides and their products across the Ileum and Rectum of the rat was studied in vitro. Peptides studied were the enkephalin fragments, Tyrosyl-Glycine, Tyrosyl-Glycyl-Glycine and Tyrosyl-Glycyl-Glycyl-Phenylalanine, and the unnatural series, Tyrosyl-D-Alanine, Tyrosyl-D-Alanyl-Glycine and Tyrosyl-D-Alanyl-Glcycyl-Phenylalanine which had D-Alanine to protect against hydrolysis. The project used or developed techniques of everted ileal and rectil sacs and rings, and estimations of Peptide hydrolase activity were made. Analytical methods used or developed were Thin Layer Chromatography with or without acid hydrolysis, scintillation counting and bioassay. Results indicate that both Dipeptides pass to the serosal side intact in ileum and rectum in a time and concentration dependent way. Mechanisms in both tissues was predominantly Sodium dependent. Hydrolase rates were higher for Tyrosyl-Glycine. Saturation of the enzymes and uptake mechanisms occurred at high mucosal Peptide concentrations, with Tyrosyl-DAlanine also showing what may be enzyme binding. Experiments with Tripeptides showed that only Tyrosyl- D-Alanyl-Glycine passed intact to the serosal fluid, either in the ileum or rectum. Hydrolase activity for Tyrosyl-Glycyl-Glycine was higher than for Tyrosyl-Glycine and the other Tripeptide. The first point of enzyme cleavage was, in both cases, at the Tyrosine to Dipeptide bonds, with D-Alanine providing protection to its Tripeptide, shown by the low hydrolysis rate. Tyrosyl-D-Alanyl-Glycine intact absorption was shown to be time and concentration dependent. Ileal absorption was mainly Sodium dependent, but was not so important in the rectum. Evidence of uptake against concentration gradients was inconclusive. Limited Tetrapeptide experiments on ileum showed only Tyrosyl-D-Alanyl-Glycyl-Phenylalanine passed intact, and this was in a time and concentration dependent way. Hydrolase activity rates for the Peptide seemed very high, but this may have been due to the experimental method. Whether uptake of this Tetrapeptide is Sodium dependent, remains inconclusive.
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