{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390282680155216640.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2133/dmpk.dmpk-14-rg-047"}},{"identifier":{"@type":"PMID","@value":"25008848"}},{"identifier":{"@type":"URI","@value":"http://api.elsevier.com/content/article/PII:S1347436715303670?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"http://api.elsevier.com/content/article/PII:S1347436715303670?httpAccept=text/plain"}},{"identifier":{"@type":"NAID","@value":"130004933553"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2015261203"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"en","@value":"Evaluation of a Thiodipeptide, L-Phenylalanyl-Ψ[CS-N]-L-alanine, as a Novel Probe for Peptide Transporter 1"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"<span style=\"font-variant: small-caps;\">l</span>-Phenylalanyl-Ψ[CS-N]-<span style=\"font-variant: small-caps;\">l</span>-alanine (Phe-Ψ-Ala), a thiourea dipeptide, was evaluated as a probe for peptide transporter 1 (PEPT1). Uptake of Phe-Ψ-Ala in PEPT1-overexpressing HeLa cells was significantly higher than that in vector-transfected HeLa cells and the <i>K</i><sub>m</sub> value was 275 ± 32 µM. The uptake was pH-dependent, being highest at pH 6.0, and was significantly decreased in the presence of PEPT1 inhibitors [glycylsarcosine (Gly-Sar), cephalexin, valaciclovir, glycylglycine, and glycylproline]. In metabolism assay using rat intestinal mucosa, rat hepatic microsomes, and human hepatocytes, the amount of Phe-Ψ-Ala was unchanged, whereas phenylalanylalanine was extensively decomposed. The clearance, distribution volume, and half-life of intravenously administered Phe-Ψ-Ala in rats were 0.151 ± 0.008 L/h/kg, 0.235 ± 0.012 L/kg, and 1.14 ± 0.07 h, respectively. The maximum plasma concentration of orally administered Phe-Ψ-Ala (2.31 ± 0.60 µg/mL) in the presence of Gly-Sar was significantly decreased compared with that in the absence of glycylsarcosine (3.74 ± 0.44 µg/mL), suggesting that the intestinal absorption of Phe-Ψ-Ala is mediated by intestinal PEPT1. In conclusion, our results indicate that Phe-Ψ-Ala is a high-affinity, metabolically stable, non-radioactive probe for PEPT1, and it should prove useful in studies of PEPT1, <i>e.g.</i>, for predicting drug-drug interactions mediated by PEPT1 <i>in vitro</i> and <i>in vivo</i>."}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420282801208722688","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"40709028"},{"@type":"NRID","@value":"1000040709028"},{"@type":"NRID","@value":"9000399835690"},{"@type":"NRID","@value":"9000411031726"},{"@type":"NRID","@value":"9000410628535"},{"@type":"NRID","@value":"9000023586423"},{"@type":"NRID","@value":"9000408789923"},{"@type":"NRID","@value":"9000257892772"},{"@type":"NRID","@value":"9000023595294"},{"@type":"NRID","@value":"9000347194079"},{"@type":"NRID","@value":"9000345289306"},{"@type":"NRID","@value":"9000360584288"},{"@type":"NRID","@value":"9000410152459"},{"@type":"NRID","@value":"9000391550693"},{"@type":"NRID","@value":"9000311506074"},{"@type":"NRID","@value":"9000243877251"},{"@type":"NRID","@value":"9000366129412"},{"@type":"NRID","@value":"9000279909385"},{"@type":"NRID","@value":"9000279912777"},{"@type":"NRID","@value":"9000382645569"},{"@type":"NRID","@value":"9000312724687"},{"@type":"NRID","@value":"9000283571524"},{"@type":"NRID","@value":"9000412195336"},{"@type":"NRID","@value":"9000347193817"},{"@type":"NRID","@value":"9000415188518"},{"@type":"NRID","@value":"9000293841144"},{"@type":"NRID","@value":"9000345267727"},{"@type":"NRID","@value":"9000415428260"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/arakawa-h"}],"foaf:name":[{"@language":"en","@value":"ARAKAWA 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Takuo"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Faculty of Pharmacy, Takasaki University of Health and Welfare"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"13474367"},{"@type":"EISSN","@value":"18800920"}],"prism:publicationName":[{"@language":"en","@value":"Drug Metabolism and Pharmacokinetics"},{"@language":"en","@value":"DMPK"},{"@language":"ja","@value":"Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society for the Study of Xenobiotics"},{"@language":"ja","@value":"日本薬物動態学会"}],"prism:publicationDate":"2014","prism:volume":"29","prism:number":"6","prism:startingPage":"470","prism:endingPage":"474"},"reviewed":"false","url":[{"@id":"http://api.elsevier.com/content/article/PII:S1347436715303670?httpAccept=text/xml"},{"@id":"http://api.elsevier.com/content/article/PII:S1347436715303670?httpAccept=text/plain"},{"@id":"https://search.jamas.or.jp/link/ui/2015261203"}],"availableAt":"2014","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=peptide%20transporter%201%20(PEPT1)","dc:title":"peptide transporter 1 (PEPT1)"},{"@id":"https://cir.nii.ac.jp/all?q=Phe-%CE%A8-Ala","dc:title":"Phe-Ψ-Ala"},{"@id":"https://cir.nii.ac.jp/all?q=Gly-Sar","dc:title":"Gly-Sar"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050848249885334528","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Stereoselective synthesis of 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