Linked Life Data

9610386

Source:http://linkedlifedata.com/resource/pubmed/id/9610386

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-6-15
pubmed:abstractText
Valacyclovir is a prodrug of the antiviral agent acyclovir and it does not contain a peptide bond in its structure. We studied the interaction of valacyclovir with the peptide transporters in the human intestinal cell line Caco-2 and the rat kidney proximal tubular cell line SKPT which differentially express peptide transporters PEPT1 and PEPT2. The results of the studies done with these cell lines were confirmed with the cloned peptide transporters human PEPT1 and rat PEPT2, expressed heterologously in HeLa cells. The activity of the peptide transporters was assessed by measuring the uptake of radiolabeled glycylsarcosine in the presence of a H+ gradient. Valacyclovir inhibited the uptake of glycylsarcosine with an inhibition constant (Ki) of 0.49 +/- 0.04 mM in Caco-2 cells and 0.17 +/- 0.01 mM in SKPT cells. In both cell types, the inhibition was competitive. Acyclovir, in contrast to valacyclovir, did not interact with the peptide transporters. Similar results were obtained with heterologously expressed human PEPT1 and rat PEPT2. Valacyclovir inhibited the hPEPT1-mediated glycylsarcosine transport competitively with a Ki value of 0.74 +/- 0.14 mM. The rPEPT2-mediated transport of glycylsarcosine was also inhibited by valacyclovir competitively and the Ki value for the process was 0.39 +/- 0.03 mM. Acyclovir did not interact with either of these cloned peptide transporters. We conclude that valacyclovir is a substrate for the peptide transporters PEPT1 and PEPT2 and that a peptide bond is not a prerequisite for recognition as a substrate by the peptide transporters.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acyclovir, http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Dipeptides, http://linkedlifedata.com/resource/pubmed/chemical/PepT1 protein, http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/SLC15A1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Slc15a1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Symporters, http://linkedlifedata.com/resource/pubmed/chemical/Valine, http://linkedlifedata.com/resource/pubmed/chemical/glycylsarcosine, http://linkedlifedata.com/resource/pubmed/chemical/hydrogen-coupled oligopeptide..., http://linkedlifedata.com/resource/pubmed/chemical/valacyclovir
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
246
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
470-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2.
pubmed:affiliation
Department of Medicine, Medical College of Georgia, Augusta 30912-2100, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.