{"_buckets": {"deposit": "475c1fc8-e6c7-427c-a912-ec74ab736c75"}, "_deposit": {"id": "2000285", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "2000285"}, "status": "published"}, "_oai": {"id": "oai:niigata-u.repo.nii.ac.jp:02000285", "sets": ["455", "562"]}, "author_link": [], "control_number": "2000285", "item_6_date_granted_51": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2021-03-23"}]}, "item_6_degree_grantor_49": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_language": "ja", "subitem_degreegrantor_name": "新潟大学"}, {"subitem_degreegrantor_language": "en", "subitem_degreegrantor_name": "Niigata University"}], "subitem_degreegrantor_identifier": [{"subitem_degreegrantor_identifier_name": "13101", "subitem_degreegrantor_identifier_scheme": "kakenhi"}]}]}, "item_6_degree_name_48": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（医学）", "subitem_degreename_language": "ja"}]}, "item_6_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Clozapine is an antipsychotic agent prescribed to psychotic patients exhibiting tolerance and/or resistance to the conventional antipsychotic medications that mainly drive monoamine antagonism. As the pharmacological fundamentals of its unique antipsychotic profile have been unrevealed, here, we attempted to obtain hints at this question. Here, we found that clozapine directly acts on ErbB kinases to downregulate epidermal growth factor (EGF)/neuregulin signaling. In cultured cell lines and cortical neurons, EGF-triggered ErbB1 phosphorylation was diminished by 30 μM clozapine, but not haloperidol, risperidone, or olanzapine. The neuregulin-1-triggered ErbB4 phosphorylation was attenuated by 10 μM clozapine and 30 μM haloperidol. We assumed that clozapine may directly interact with the ErbB tyrosine kinases and affect their enzyme activity. To test this assumption, we performed in vitro kinase assays using recombinant truncated ErbB kinases. Clozapine (3–30 μM) significantly decreased the enzyme activity of the truncated ErbB1, B2, and B4 kinases. Acute in vivo administration of clozapine (20 mg/kg) to adult rats significantly suppressed the basal phosphorylation levels of ErbB4 in the brain, although we failed to detect effects on basal ErbB1 phosphorylation. Altogether with the previous findings that quinazoline inhibitors for ErbB kinases harbor antipsychotic potential in animal models for schizophrenia, our present observations suggest the possibility that the micromolar concentrations of clozapine can attenuate the activity of ErbB receptor kinases, which might illustrate a part of its unique antipsychotic psychopharmacology.", "subitem_description_language": "en", "subitem_description_type": "Abstract"}]}, "item_6_description_5": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "Translational Psychiatry. 2019, 9, 181.", "subitem_description_language": "en", "subitem_description_type": "Other"}]}, "item_6_description_53": {"attribute_name": "学位記番号", "attribute_value_mlt": [{"subitem_description": "新大院博(医)第980号", "subitem_description_language": "ja", "subitem_description_type": "Other"}]}, "item_6_dissertation_number_52": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "甲第4826号"}]}, "item_6_relation_14": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1038/s41398-019-0519-1", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_15": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "【○!C】 The Author(s) 2019", "subitem_rights_language": "en"}, {"subitem_rights": "Creative Commons Attribution 4.0 International", "subitem_rights_language": "en", "subitem_rights_resource": "https://creativecommons.org/licenses/by/4.0/"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "open access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_abf2"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Kobayashi, Yutaro", "creatorNameLang": "en"}, {"creatorName": "小林, 雄太朗", "creatorNameLang": "ja"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"date": [{"dateType": "Available", "dateValue": "2022-04-04"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "r2nmk980.pdf", "filesize": [{"value": "1.43MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": "1.43MB", "url": {"label": "本文", "objectType": "fulltext", "url": "https://niigata-u.repo.nii.ac.jp/record/2000285/files/r2nmk980.pdf"}, "version_id": "ac10b7eb-6160-4fb6-bf44-da1e6766849a"}, {"date": [{"dateType": "Available", "dateValue": "2022-04-04"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "r2nmk980_a.pdf", "filesize": [{"value": "559KB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": "559KB", "url": {"label": "要旨", "objectType": "abstract", "url": "https://niigata-u.repo.nii.ac.jp/record/2000285/files/r2nmk980_a.pdf"}, "version_id": "0a59ccbd-6e50-4b62-8b2c-b7e485fda802"}]}, "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": "Clozapine-dependent inhibition of EGF/neuregulin receptor (ErbB) kinases", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Clozapine-dependent inhibition of EGF/neuregulin receptor (ErbB) kinases", "subitem_title_language": "en"}, {"subitem_title": "EGF/ニューレグリン受容体キナーゼのクロザピン依存的抑制", "subitem_title_language": "ja"}]}, "item_type_id": "6", "owner": "1", "path": ["455", "562"], "permalink_uri": "http://hdl.handle.net/10191/0002000285", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2022-04-04"}, "publish_date": "2022-04-04", "publish_status": "0", "recid": "2000285", "relation": {}, "relation_version_is_last": true, "title": ["Clozapine-dependent inhibition of EGF/neuregulin receptor (ErbB) kinases"], "weko_shared_id": -1}