Linked Life Data

9092716

Source:http://linkedlifedata.com/resource/pubmed/id/9092716

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-4-29
pubmed:abstractText
The present study was undertaken to investigate the interaction of anionic cephalosporins (cefixime, ceftibuten, and cefdinir) with the renal peptide transporter (PEPT 2) and the intestinal peptide transporter (PEPT 1) using four different experimental model systems. In the first approach, the human colon carcinoma cell line Caco-2 which expresses PEPT 1 and the SHR rat kidney cell line SKPT which expresses PEPT 2 were used. The uptake of the dipeptide Gly-Sar mediated by PEPT 1 or PEPT 2 in these cells was inhibited significantly by the anionic cephalosporins, with the following order of potency: ceftibuten > cefixime > cefdinir. The inhibition was competitive in nature. Even though the order of potency was the same for PEPT 1 and PEPT 2, PEPT 1 exhibited much lesser sensitivity to inhibition than PEPT 2. In the second approach, the cloned human PEPT 1 and PEPT 2 were functionally expressed in HeLa cells following which the cells were used to study the interaction of anionic cephalosporins with PEPT 1 and PEPT 2. Again, Gly-Sar uptake mediated by the human PEPT 1 and PEPT 2 in HeLa cells was found to be inhibited by the anionic cephalosporins with the same order potency as in Caco-2 and SKPT cells. In the third approach, brush border membrane vesicles isolated from rat kidneys were employed. In this approach also it was found that PEPT 2-mediated Gly-Sar uptake was inhibited by cefixime and ceftibuten. In the fourth approach, the human PEPT 1 was expressed in Xenopus laevis oocytes and PEPT 1-mediated transport of ceftibuten was investigated directly by electrophysiological methods. Ceftibuten evoked inward currents in PEPT 1-expressing oocytes but not in water-injected oocytes, showing that the transport of the anionic cephalosporin via PEPT 1 is associated with transfer of positive charge. The ceftibuten-evoked currents were saturable with respect to ceftibuten concentration and were markedly dependent on membrane potential. It is concluded that anionic cephalosporins interact with the peptide transporters expressed in the intestine (PEPT 1) as well as in the kidney (PEPT 2).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
1324
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
296-308
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9092716-Animals, pubmed-meshheading:9092716-Biological Transport, pubmed-meshheading:9092716-Caco-2 Cells, pubmed-meshheading:9092716-Carrier Proteins, pubmed-meshheading:9092716-Cell Line, pubmed-meshheading:9092716-Cephalosporins, pubmed-meshheading:9092716-Colon, pubmed-meshheading:9092716-Dipeptides, pubmed-meshheading:9092716-Evoked Potentials, pubmed-meshheading:9092716-HeLa Cells, pubmed-meshheading:9092716-Humans, pubmed-meshheading:9092716-Kidney, pubmed-meshheading:9092716-Microvilli, pubmed-meshheading:9092716-Oocytes, pubmed-meshheading:9092716-Rats, pubmed-meshheading:9092716-Rats, Inbred SHR, pubmed-meshheading:9092716-Rats, Sprague-Dawley, pubmed-meshheading:9092716-Symporters, pubmed-meshheading:9092716-Transfection, pubmed-meshheading:9092716-Xenopus laevis
pubmed:year
1997
pubmed:articleTitle
Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2.
pubmed:affiliation
Department of Medicine, Medical College of Georgia, Augusta 30912, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.