{"_buckets": {"deposit": "6ae39a03-f5b3-49ba-8aea-ac395de6a92f"}, "_deposit": {"id": "20108", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "20108"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00020108", "sets": ["883"]}, "author_link": ["106332", "106333", "106334", "106335"], "item_1628147817048": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_ab4af688f83e57aa", "subitem_version_type": "AM"}]}, "item_6_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2014-05-25", "bibliographicIssueDateType": "Issued"}, "bibliographicPageEnd": "68", "bibliographicPageStart": "62", "bibliographicVolumeNumber": "215", "bibliographic_titles": [{"bibliographic_title": "CHEMICO-BIOLOGICAL INTERACTIONS"}]}]}, "item_6_description_20": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "We previously demonstrated that cannabidiol (CBD) was a potent mechanism-based inhibitor of human cytochrome P450 1A1 (CYP1A1). However, the moiety of CBD that contributes to the potent mechanism-based inhibition of human CYP1A1 remains unknown. Thus, the effects of compounds structurally related to CBD on CYP1A1 activity were examined with recombinant human CYP1A1 in order to characterize the structural requirements for potent inactivation by CBD. When preincubated in the presence of NADPH for 20 min, olivetol, which corresponds to the pentylresorcinol moiety of CBD, enhanced the inhibition of the 7-ethoxyresorufin O-deethylase activity of CYP1A1. In contrast, d-limonene, which corresponds to the terpene moiety of CBD, failed to inhibit CYP1A1 activity in a metabolism-dependent manner. Pentylbenzene, which lacks two free phenolic hydroxyl groups, also did not enhance CYP1A1 inhibition. On the other hand, preincubation of the CBD-2′-monomethyl ether (CBDM) and CBD-2′,6′-dimethyl ether (CBDD) enhanced the inhibition of CYP1A1 activity. Inhibition by cannabidivarin (CBDV), which possessed a propyl side chain, was strongly potentiated by its preincubation. Orcinol, which has a methyl group, augmented CYP1A1 inhibition, whereas its derivative without an alkyl side chain, resorcinol, did not exhibit any metabolism-dependent inhibition. The preincubation of CBD-hydroxyquinone did not markedly enhance CYP1A1 inhibition. We further confirmed that olivetol, CBDM, CBDD, CBDV, and orcinol, as well as CBD (kinact = 0.215 min−1), inactivated CYP1A1 activity; their kinact values were 0.154, 0.0638, 0.0643, 0.226, and 0.0353 min−1, respectively. These results suggest that the methylresorcinol structure in CBD may have structurally important roles in the inactivation of CYP1A1.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "CHEMICO-BIOLOGICAL INTERACTIONS.215:62-68(2014)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "信州大学研究者総覧へのリンク", "attribute_value_mlt": [{"subitem_link_text": "Yamaori, Satoshi", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.jefNgUkh.html"}]}, "item_6_link_67": {"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=000336357600009"}]}, "item_6_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "ELSEVIER IRELAND LTD"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "24667653"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://www.ncbi.nlm.nih.gov/pubmed/24667653", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1016/j.cbi.2014.03.007"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1016/j.cbi.2014.03.007", "subitem_relation_type_select": "DOI"}}]}, "item_6_select_64": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "author"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0009-2797", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0009-2797", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_40": {"attribute_name": "書誌レコードID", "attribute_value_mlt": [{"subitem_source_identifier": "AA0060252X", "subitem_source_identifier_type": "NCID"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Cannabidiol; CYP1A1; Inactivation; Mechanism-based inhibition; Structural requirement"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "POLYCYCLIC AROMATIC-HYDROCARBONS; P450 1A1; MAJOR PHYTOCANNABINOIDS; HUMAN LUNG; IN-VIVO; 1B1; MARIJUANA; ACTIVATION; ENZYMES; INACTIVATION"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "We previously demonstrated that cannabidiol (CBD) was a potent mechanism-based inhibitor of human cytochrome P450 1A1 (CYP1A1). However, the moiety of CBD that contributes to the potent mechanism-based inhibition of human CYP1A1 remains unknown. Thus, the effects of compounds structurally related to CBD on CYP1A1 activity were examined with recombinant human CYP1A1 in order to characterize the structural requirements for potent inactivation by CBD. When preincubated in the presence of NADPH for 20 min, olivetol, which corresponds to the pentylresorcinol moiety of CBD, enhanced the inhibition of the 7-ethoxyresorufin O-deethylase activity of CYP1A1. In contrast, d-limonene, which corresponds to the terpene moiety of CBD, failed to inhibit CYP1A1 activity in a metabolism-dependent manner. Pentylbenzene, which lacks two free phenolic hydroxyl groups, also did not enhance CYP1A1 inhibition. On the other hand, preincubation of the CBD-2\u0027-monomethyl ether (CBDM) and CBD-2\u0027,6\u0027-dimethyl ether (CBDD) enhanced the inhibition of CYP1A1 activity. Inhibition by cannabidivarin (CBDV), which possessed a propyl side chain, was strongly potentiated by its preincubation. Orcinol, which has a methyl group, augmented CYP1A1 inhibition, whereas its derivative without an alkyl side chain, resorcinol, did not exhibit any metabolism-dependent inhibition. The preincubation of CBD-hydroxyquinone did not markedly enhance CYP1A1 inhibition. We further confirmed that olivetol, CBDM, CBDD, CBDV, and orcinol, as well as CBD (k(inact) = 0.215 min(-1)), inactivated CYP1A1 activity; their k(inact) values were 0.154, 0.0638, 0.0643, 0.226, and 0.0353 min(-1), respectively. These results suggest that the methylresorcinol structure in CBD may have structurally important roles in the inactivation of CYP1A1. (C) 2014 Elsevier Ireland Ltd. All rights reserved."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Yamaori, Satoshi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106332", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Okushima, Yoshimi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106333", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yamamoto, Ikuo", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106334", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Watanabe, Kazuhito", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106335", "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": "2018-09-18"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "Manuscript (CBI 2014 Yamaori).pdf", "filesize": [{"value": "1.5 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 1500000.0, "url": {"label": "Manuscript (CBI 2014 Yamaori).pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/20108/files/Manuscript (CBI 2014 Yamaori).pdf"}, "version_id": "9a43cca3-c0d5-4d3b-b403-e8b87a87e917"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Cannabidiol", "subitem_subject_scheme": "Other"}, {"subitem_subject": "CYP1A1", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Inactivation", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Mechanism-based inhibition", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Structural requirement", "subitem_subject_scheme": "Other"}]}, "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": "Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["883"], "permalink_uri": "http://hdl.handle.net/10091/00020869", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2018-09-18"}, "publish_date": "2018-09-18", "publish_status": "0", "recid": "20108", "relation": {}, "relation_version_is_last": true, "title": ["Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol"], "weko_shared_id": -1}