{"created":"2023-07-27T06:50:17.244942+00:00","id":43009,"links":{},"metadata":{"_buckets":{"deposit":"fa8ae7f3-e948-49a2-bddb-b584c743b5ad"},"_deposit":{"created_by":18,"id":"43009","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"43009"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00043009","sets":["2812:2813:2837"]},"author_link":["69193","69199"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"1997-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"10p.","bibliographicVolumeNumber":"1995-1996","bibliographic_titles":[{"bibliographic_title":"平成8(1996)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"1996 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"目的:「担体介在輸送・排出」による外因性物質選択的脳移行制御機構がダイナミックインターフェース(DIF)としての血液脳関門(BBB)機能を担っているというBBBの実体に迫る我々の独創的仮説の実証を行うことを目的とした。結果:1.ラット脳虚血による脳内ATP量の低下は、〔^<14>C〕sucroseの脳透過係数(PS)に変化を与えず、doxorubisin (DOX)のPSを正常時の17倍に増加させたが、この値は血流再灌流によって回復した。また初代培養ウシ脳毛細血管内皮細胞(BCECs)内のATP量の減少に伴って、DOXのBCEC内蓄積量の増大が観測された。以上の結果とこれまでの結果と合わせ、一次性排出ポンプP-糖蛋白質(P-gp)によってDOXなど脂溶性薬物の脳内移行が著しく制限されていることを実証できた。2.BCECsの血液側膜及び脳側膜からの〔^3H〕β-alanineおよび〔^3H〕taurineの輸送に対する温度・代謝エネルギー依存症、Na^+・Cl^-勾配依存症ATP枯褐BCECsにおけるカウンタートランスポート効果や各種アミノ酸による阻害様式から、BBBにはtaurineを二次性能動輸送するβ-alanine輸送系が存在することを初めて明らかにすることができた。3.H^+/モノカルボン酸共輸送系MCT1が、BCECにも発現していることをRT-PCR法によって確認し、その塩基配列が小腸のそれと一致することを認めた。このMCT1が血液脳間のモノカルボン酸化合物交換を制御していると思われる。4.ペプチドが塩基性と脂溶性のバランスに依存してadsorptive-mediated endocytosis(AME)機構でBCECsに取り込まれることを明らかにした。結論:薬物の中枢移行性は、分子の脂溶性によって制御されるほかに、BCECに発現する種々の輸送系に対する認識特性に依存し、P-gpによる排出機能によっても制御されるという、DFIとしての新しいBBBの概念を指示することができた。また、本研究により中枢作用型ペプチド医薬品の設計にAME機構を利用する道が開かれた。","subitem_description_type":"Abstract"},{"subitem_description":"The purpose of this research project is to clarify the blood-brain barrier (BBB) functions by regulating carrier-mediated influx and efflux of nutrients and xenobiotics. The following results were obtained by two years term of this research project :\n1.In transient brain ischemic rats, ATP depletion in the brain resulted in the 17-fold increase of BBB permeability coefficient (PS) of doxorubicin (DOX), whereas no change of PS-value of sucrose by this ischemia. When the ATP content recovered to a normal level by means of cerebral recirculation of blood, the PS-value of DOX recovered to the control PS-value in normal rats. The uptake of DOX by primary cultured bovine brain capillary endothelial cells (BCECs) expressing P-glycoprotein (P-gp) at the luminal membrane was increased significantly by the depletion of ATP level in BCECs. Present evidence for the ATP-dependent transport of DOX and previous results from our laboratory strongly indicate that P-gp in the brain capillaries functions actively as an efflux pump for lipophilic xenobiotics, providing a major mechanism to restrict the transfer of xenobiotics as well as DOX in the brain.\n2.Secondary active transport system for beta-alanine and taurine, which are transported in sodium and chloride-ion dependent manner, functions at both the luminal and antiluminal membranes of the BBB.The transport system was highly selective for beta-amino acids, such as beta-alanine, taurine and hypotaurine.\n3.The expression of H^+/monocarboxylate transporter MCT1 in the brain capillaries was clarified by RT-PCR and the nucleotide sequence of the PCR product was confirmed to be the same as that of a part of ratMCT1. This result indicates that MCT1 contributes to pH-dependent and carrier-mediated influx and efflux of monocarboxylic acids at the BBB.\n4.Peptides were confirmed to be taken up by BCECs via adsorptive-mediated endocytosis which was affected by charge density and/or lipophilicity of peptides.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:07457527, 研究期間(年度):1995-1996","subitem_description_type":"Other"},{"subitem_description":"出典：「ダイナミックインターフェイスとしての血液脳関門機能と薬物脳移行相関」研究成果報告書　課題番号07457527\n(KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00049358","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学自然科学研究科"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=10019664"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=10019664","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457527/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457527/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-07457527/074575271996kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-07457527/074575271996kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-12-11"}],"displaytype":"detail","filename":"PH-PR-TSUJI-A-kaken 1997B-10p.pdf","filesize":[{"value":"220.9 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"PH-PR-TSUJI-A-kaken 1997B-10p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/43009/files/PH-PR-TSUJI-A-kaken 1997B-10p.pdf"},"version_id":"4e5817e2-6607-4154-8ae7-bd05d942771f"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"ダイナミックインターフェイスとしての血液脳関門機能と薬物脳移行相関","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"ダイナミックインターフェイスとしての血液脳関門機能と薬物脳移行相関"},{"subitem_title":"Blood-brain barrier functioning as dynamic interface and drug delivery to the brain","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2837"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-12-14"},"publish_date":"2017-12-14","publish_status":"0","recid":"43009","relation_version_is_last":true,"title":["ダイナミックインターフェイスとしての血液脳関門機能と薬物脳移行相関"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:53:41.806720+00:00"}