{"_buckets": {"deposit": "bb647f81-8ba2-4b7a-b3f7-01a266860b65"}, "_deposit": {"id": "21390", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "21390"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00021390", "sets": ["849"]}, "author_link": ["109517"], "item_14_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2019-03-31", "bibliographicIssueDateType": "Issued"}}]}, "item_14_date_granted_8": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2019-03-31"}]}, "item_14_degree_grantor_10": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "信州大学(Shinshu university)"}]}]}, "item_14_degree_name_9": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（医学）"}]}, "item_14_description_26": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "雑誌に発表。CHEMICO-BIOLOGICAL INTERACTIONS. 306:1-9 (2019); doi:10.1016/j.cbi.2019.04.005.", "subitem_description_type": "Other"}]}, "item_14_description_37": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Thesis", "subitem_description_type": "Other"}]}, "item_14_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "池村　憲明. Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity : potent inhibition by azelnidipine and manidipine （シトクロムP450 2J2に対する降圧薬の阻害効果：アゼルニジピンとマニジピンによる強力な阻害）. 信州大学, 2019, 博士論文.", "subitem_description_type": "Other"}]}, "item_14_dissertation_number_7": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "13601甲第1180号"}]}, "item_14_link_74": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000468517400001"}]}, "item_14_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "信州大学"}]}, "item_14_relation_54": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "30965050"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search\u0026DB=pubmed\u0026term=30965050", "subitem_relation_type_select": "PMID"}}]}, "item_14_relation_55": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1016/j.cbi.2019.04.005"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1016/j.cbi.2019.04.005", "subitem_relation_type_select": "DOI"}}]}, "item_14_rights_69": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/"}]}, "item_14_select_71": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_14_text_11": {"attribute_name": "学位の区分", "attribute_value_mlt": [{"subitem_text_value": "Doctoral"}]}, "item_14_text_12": {"attribute_name": "学位の分野", "attribute_value_mlt": [{"subitem_text_value": "医学"}]}, "item_14_text_13": {"attribute_name": "学位の報告番号", "attribute_value_mlt": [{"subitem_text_value": "甲第1180号"}]}, "item_14_text_76": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Cytochrome P450 2J2; Antihypertensive drugs; Inhibition; Inactivation; Docking simulation"}]}, "item_14_text_77": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "ANTITUMOR-ACTIVITY; IN-VITRO; CYP2J2; EXPRESSION; METABOLISM; PROMOTES; INACTIVATION; INVOLVEMENT; SUBSTRATE; CELLS"}]}, "item_14_textarea_75": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "The inhibitory effects of antihypertensive drugs (dihydropyridine calcium channel blockers, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors) on cytochrome P450 2J2 (CYP2J2) activity were examined. Amlodipine, azelnidipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nisoldipine, nitrendipine, telmisartan, delapril, and quinapril inhibited luciferin-2J2/4F12 O-dealkylase activity of recombinant human CYP2J2 in a concentration-dependent manner (IC50 = 0.116-9.19 mu M). Kinetic analyses of the inhibition indicated that azelnidipine, barnidipine, benidipine, cilnidipine, efonidipine, manidipine, nicardipine, telmisartan, delapril, and quinapril competitively inhibited CYP2J2 activity, while amlodipine, felodipine, nifedipine, nilvadipine, nisoldipine, and nitrendipine showed mixed inhibition. Among these drugs, manidipine showed the strongest reversible inhibition with K-i value of 0.0294 mu M. The docking simulation data supported the potent inhibition of CYP2J2 by these drugs. Next, the effect of preincubation on CYP2J2 inhibition was investigated to determine whether these antihypertensive drugs inhibited CYP2J2 activity in a metabolism-dependent manner. A 20-min preincubation of azelnidipine and felodipine in the presence of NADPH potentiated the inhibition of CYP2J2. Furthermore, kinetic analysis of the inactivation showed that azelnidipine caused a preincubation time-and concentration-dependent decrease in CYP2J2 activity yielding k(inact)/K-I value of 105 l/mmol/min, although felodipine showed no preincubation time-dependent inhibition. The azelnidipine-mediated inactivation required NADPH. These results indicated that manidipine is a potent competitive reversible inhibitor while azelnidipine is a potent mechanism-based inactivator of human CYP2J2."}]}, "item_1627890986942": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_be7fb7dd8ff6fe43", "subitem_version_type": "NA"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "池村, 憲明"}], "nameIdentifiers": [{"nameIdentifier": "109517", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "15MH001H_yoshi.pdf", "filesize": [{"value": "163.6 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 163600.0, "url": {"label": "内容の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21390/files/15MH001H_yoshi.pdf"}, "version_id": "225e70e1-892a-49fd-beb2-46edfbab07b8"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "15MH001H_shinsa.pdf", "filesize": [{"value": "140.4 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 140400.0, "url": {"label": "審査結果の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21390/files/15MH001H_shinsa.pdf"}, "version_id": "b5407271-23c0-4147-ad6e-a924c145760e"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "15MH001H_ronbun.pdf", "filesize": [{"value": "427.8 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/", "licensetype": "license_note", "mimetype": "application/pdf", "size": 427800.0, "url": {"label": "博士論文の全文", "url": "https://soar-ir.repo.nii.ac.jp/record/21390/files/15MH001H_ronbun.pdf"}, "version_id": "e7ae8a11-e744-45f6-86dc-6bf907e8f4cb"}]}, "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": "doctoral thesis", "resourceuri": "http://purl.org/coar/resource_type/c_db06"}]}, "item_title": "Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity : potent inhibition by azelnidipine and manidipine （シトクロムP450 2J2に対する降圧薬の阻害効果：アゼルニジピンとマニジピンによる強力な阻害）", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity : potent inhibition by azelnidipine and manidipine （シトクロムP450 2J2に対する降圧薬の阻害効果：アゼルニジピンとマニジピンによる強力な阻害）", "subitem_title_language": "en"}]}, "item_type_id": "14", "owner": "1", "path": ["849"], "permalink_uri": "http://hdl.handle.net/10091/00022147", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2020-06-15"}, "publish_date": "2020-06-15", "publish_status": "0", "recid": "21390", "relation": {}, "relation_version_is_last": true, "title": ["Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity : potent inhibition by azelnidipine and manidipine （シトクロムP450 2J2に対する降圧薬の阻害効果：アゼルニジピンとマニジピンによる強力な阻害）"], "weko_shared_id": -1}