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- W2339247389 abstract "Oligopeptide transport in rat small intestine has been studied in intact tissue,using the luminally and vascularly perfused isolated jejunum in situ technique, and ahydrolysis-resistant dipeptide (D-Phe-L-Gln). The data in this thesis can be dividedinto two main sections: (l) identification of the transporter proteins, and (2)short-term regulation of transport.The basolateral peptide transporter protein has not, to date, been identified. Acandidate protein was identified from membrane vesicles by a photo affinity labellingtechnique using a dipeptide derivative ([4-azido-3,5-3H-D-Phe]-L-Ala), previouslyshown to be an efficient substrate for the basolateral transporter. The labelledcandidate protein was successfully isolated by 2-DE, which revealed an apparent Mrof 112 ± 2 kDa and a pI of approximately 6.5. Initial sequence analysis, trypticdigestion followed by MALDI-TOF analysis and Q-TOF fragmentation of a trypticpeptide, produced a peptide fingerprint and a sequence tag of 9 amino acids,respectively, which, together, did not completely and conclusively match to anyknown protein sequence contained within databases, therefore suggesting that the112 kDa protein may be novel.Short-term regulation of peptide transport was also investigated using thevascular perfusion method. An amino acid-sensing pathway was discovered, usingL-Leucine as the regulator, involving protein kinase cacades leading to p70S6kactivation and subsequent stimulation ofbasolateral membrane peptide transport.A major conclusion arising from the data was the distinction between PepTland the basolateral transporter, i.e. the sequence data obtained from the candidateprotein did not match to the PepTl sequence; in addition there appeared to be distinctmechanisms of regulatory control at the two membranes.Efficient delivery of peptidomimetic drugs when adminsitered by the oralroute requires knowledge of short-term regulation of intestinal peptide transport, inaddition to the sequence and structure of the basolateral transporter. This thesisprovides essential information, which may eventually contribute to the unequivocalidentification and sequencing of the intestinal basolateral peptide transporter, ultimately leading to the future development of compounds with high bioavailability." @default.
- W2339247389 created "2016-06-24" @default.
- W2339247389 creator A5003920761 @default.
- W2339247389 date "2001-01-01" @default.
- W2339247389 modified "2023-09-24" @default.
- W2339247389 title "Oligopeptide transport across the basolateral membrane of rat small intestine" @default.
- W2339247389 hasPublicationYear "2001" @default.
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