Source:http://linkedlifedata.com/resource/pubmed/id/17142565
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-2-27
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pubmed:abstractText |
Gastrointestinal absorption of the beta-lactam antibiotic cephalexin (CEX) is highly stereoselective: l- and d-CEX are both taken up by intestinal epithelial cells through the brush-border membrane, most likely via oligopeptide transporter PEPT1, but l-CEX is not found in serum or urine after administration p.o. because of its rapid intestinal metabolism, whereas d-CEX is well absorbed in the unchanged form. We examined the contribution of PEPT1 to the stereoselective uptake and metabolism of CEX. We observed stereoselective metabolism of CEX after exogenous transfection of PEPT1 alone into mammalian cell lines: l-CEX, but not d-CEX, was metabolized to 7-aminodesacetoxycephalosporanic acid (7-ADCA) in HeLa and human embryonic kidney 293 cells stably and transiently expressing human PEPT1, respectively, whereas such metabolism was minor in cells expressing the vector alone. The formation rate of 7-ADCA depended on the amount of PEPT1 cDNA transfected. l-CEX metabolism was rapid because only 7-ADCA was found inside and outside the cells during incubation with l-CEX. The characteristics of PEPT1-mediated metabolism of l-CEX were similar, but not identical, to those of PEPT1-mediated transport. PEPT1-mediated metabolism was also observed in permeabilized cells expressing PEPT1, in which PEPT1-mediated intracellular substrate accumulation was negligible, suggesting that the increase in l-CEX metabolism by PEPT1 transfection cannot be fully explained by an increase in uptake and subsequent exposure to intracellular hydrolases. The present findings show that stereoselectivity in CEX absorption can be fully explained in terms of PEPT1, implying that the l-CEX hydrolase is PEPT1 itself or is induced by PEPT1.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cephalexin,
http://linkedlifedata.com/resource/pubmed/chemical/L-Lactate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/SLC15A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0090-9556
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
356-62
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pubmed:meshHeading |
pubmed-meshheading:17142565-Anti-Bacterial Agents,
pubmed-meshheading:17142565-Cephalexin,
pubmed-meshheading:17142565-HeLa Cells,
pubmed-meshheading:17142565-Humans,
pubmed-meshheading:17142565-L-Lactate Dehydrogenase,
pubmed-meshheading:17142565-Symporters,
pubmed-meshheading:17142565-Transfection
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pubmed:year |
2007
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pubmed:articleTitle |
Functional expression of stereoselective metabolism of cephalexin by exogenous transfection of oligopeptide transporter PEPT1.
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pubmed:affiliation |
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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