{"created":"2023-07-27T06:30:21.278786+00:00","id":15342,"links":{},"metadata":{"_buckets":{"deposit":"0494b3b1-ddef-4b74-a838-b59c4cc1d1cf"},"_deposit":{"created_by":3,"id":"15342","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"15342"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00015342","sets":["1132:1133:1135"]},"author_link":["21623","27833","21465","27834","29","34","27835"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-08-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"8","bibliographicPageEnd":"1461","bibliographicPageStart":"1459","bibliographicVolumeNumber":"32","bibliographic_titles":[{"bibliographic_title":"Biological and Pharmaceutical Bulletin"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The oligopeptide transporter PEPT1 (SLC15A1) is responsible for absorption of peptidic nutrients in the small intestine. Although the L-diastereomer of the β-lactam antibiotic cephalexin (L-cephalexin) is likely to be transported by PEPT1, there has been no direct demonstration of PEPT1-mediated L-cephalexin transport. Indeed, after the incubation with L-cephalexin, the intact form of L-cephalexin has not been identified inside vesicles/proteoliposomes prepared from brush border membrane of intestinal epithelial cells or cultured cell lines exogenously transfected with PEPT1 gene. Thus, it appears that L-cephalexin is rapidly metabolized by PEPT1 or PEPT1-associated proteins. Here, we attempted to verify whether L-cephalexin is transported by PEPT1 and whether it is hydrolyzed by PEPT1 itself, by using budded baculovirus expressing PEPT1 protein. Marked uptake of L-cephalexin in PEPT1-expressing budded baculovirus, compared with wild-type virus, indicated that L-cephalexin is a substrate for PEPT1. The uptake was found to be pH sensitive, and was strongly inhibited by the D-diastereomer of cephalexin and glycylsarcosine, but not by glycine. Thus, L-cephalexin is transported by PEPT1 itself. Upon the transport of both L- and D-cephalexin by PEPT1, dose-dependent membrane depolarization was observed; the EC50 values of 0.18 and 2.9 mM, respectively, indicate that the affinity of L-cephalexin for PEPT1-mediated transport is much higher than that of the D-diastereomer. On the other hand, the L-cephalexin metabolite 7-aminodesacetoxycephalosporanic acid was not detected in PEPT1-expressing or wild-type virus at either pH 6.0 or 7.4. We conclude that L-cephalexin is transported by PEPT1 with high affinity, but is not metabolized by PEPT1 itself. © 2009 Pharmaceutical Society of Japan.","subitem_description_type":"Abstract"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Pharmaceutical Society of Japan = 日本薬学会"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1248/bpb.32.1459","subitem_relation_type_select":"DOI"}}]},"item_4_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.jstage.jst.go.jp/article/bpb/32/8/32_1459/_article","subitem_relation_type_select":"URI"}}]},"item_4_rights_23":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"(c) 2009 The Pharmaceutical Society of Japan"}]},"item_4_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AA10885497","subitem_source_identifier_type":"NCID"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0918-6158","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Mitsuoka, Keisuke"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tamai, Ikumi"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Morohashi, Yasushi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kubo, Yoshiyuki"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Saitoh, Ryoichi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tsuji, Akira"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Kato, Yukio"}],"nameIdentifiers":[{},{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-04"}],"displaytype":"detail","filename":"PH-PR-KATO-Y-1459.pdf","filesize":[{"value":"80.0 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"PH-PR-KATO-Y-1459.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/15342/files/PH-PR-KATO-Y-1459.pdf"},"version_id":"be6f7086-434c-4fb8-9134-dbaf710ab869"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Direct evidence for efficient transport and minimal metabolism of L-cephalexin by oligopeptide transporter 1 in budded baculovirus fraction","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Direct evidence for efficient transport and minimal metabolism of L-cephalexin by oligopeptide transporter 1 in budded baculovirus fraction"}]},"item_type_id":"4","owner":"3","path":["1135"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-04"},"publish_date":"2017-10-04","publish_status":"0","recid":"15342","relation_version_is_last":true,"title":["Direct evidence for efficient transport and minimal metabolism of L-cephalexin by oligopeptide transporter 1 in budded baculovirus fraction"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-28T00:33:58.361029+00:00"}