{"created":"2023-06-20T14:26:02.524826+00:00","id":1291,"links":{},"metadata":{"_buckets":{"deposit":"3683642f-2087-4955-8219-41f8b2e84d90"},"_deposit":{"created_by":3,"id":"1291","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"1291"},"status":"published"},"_oai":{"id":"oai:dmu.repo.nii.ac.jp:00001291","sets":["81:77"]},"author_link":["6411","6410","6406","6408","6405","6409","6404","6414","6412","6407","6403","6413"],"item_2_biblio_info_12":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-03-25","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"29","bibliographicPageStart":"23","bibliographicVolumeNumber":"43","bibliographic_titles":[{"bibliographic_title":"Dokkyo journal of medical sciences"}]}]},"item_2_description_11":{"attribute_name":"抄録(英)","attribute_value_mlt":[{"subitem_description":"Hyperuricemia has recently been recognized as one of the risk factors for cardiovascular diseases. Some calcium channel blockers(CCBs), commonly used in the treatment of hypertension, have been reported to decrease serum urate level. Here, we tried to elucidate the molecular mechanism of the urate-lowering effects of CCBs. We performed [^<14>C]urate uptake in cells stably expressing human urate transporter 1, a major contributor of renal urate reabsorption and a major target of uricosuric drugs such as benzbromarone and losartan(HEK-URAT1), together with mock(HEK-mock)cells to analyze the uricosuric action of CCBs. We also measured the activity of human xanthine oxidase(XO)to determine whether CCBs have inhibitory effects on urate production. The CCBs tested were nifedipine, nilvadipine, nitrendipine, benidipine, nisoldipine, nicardipine, efonidipine, amlodipine, azelnidipine, verapamil and diltiazem. We found for the first time that at least seven CCBs in the dihydropyridine subgroup interacted with URAT1-mediated urate uptake in HEK-URAT1 cells. Among these CCBs, nifedipine, nilvadipine and nitrendipine strongly inhibited URAT1-mediated urate uptake. Their IC_<50>s were 15.8, 0.018 and 0.40?μM, respectively. In contrast, urate production mediated by XO was weakly inhibited by nifedipine and nisoldipine. In summary, URAT1 interacted with various CCBs differently, whereas XO, a major enzyme for urate production in the liver, did not interact with most of CCBs. Although CCBs were not excreted from the urine basically, their urate-lowering effects may be associated with the inhibition of renal urate reabsorption mediated by renal urate transporters such as URAT1 with their metabolites, and the results for structure-activity information in this study will provide a clue for developing new uricosuric drugs targeting URAT1.","subitem_description_type":"Other"}]},"item_2_description_9":{"attribute_name":"記事種別(英)","attribute_value_mlt":[{"subitem_description":"Original","subitem_description_type":"Other"}]},"item_2_source_id_1":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AA00629581"}]},"item_2_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"03855023","subitem_source_identifier_type":"ISSN"}]},"item_2_text_7":{"attribute_name":"著者所属(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Material And Environmental Chemistry, Graduate School Of Engineering, Utsunomiya Niversity:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"},{"subitem_text_language":"en","subitem_text_value":"Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine"}]},"item_2_title_3":{"attribute_name":"論文名よみ","attribute_value_mlt":[{"subitem_title":"Molecular Mechanism of the Urate-lowering Effects of Calcium Channel Blockers"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Tsuchiya, Go","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hori, Takayuki","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Onizawa, Nobuyuki","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Otani, Naoyuki","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tanaka-nakadate, Sawako","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Iseki, Tatou","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ouchi, Motoshi","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hayashi, Keitaro","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Jutabha, Promsuk","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Oba, Toru","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Fukuda, Hirotsugu","creatorNameLang":"en"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Anzai, Naohiko","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-05-24"}],"displaytype":"detail","filename":"KJ00010141602.pdf","filesize":[{"value":"310.4 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"KJ00010141602.pdf","url":"https://dmu.repo.nii.ac.jp/record/1291/files/KJ00010141602.pdf"},"version_id":"4a983bce-0948-4a23-b53f-665f467b5b0f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Calcium Channel Blockers","subitem_subject_language":"en"},{"subitem_subject":"Uricosuric Drugs","subitem_subject_language":"en"},{"subitem_subject":"Urate","subitem_subject_language":"en"},{"subitem_subject":"Transporters","subitem_subject_language":"en"},{"subitem_subject":"Urat1","subitem_subject_language":"en"},{"subitem_subject":"Xanthine Oxidase","subitem_subject_language":"en"}]},"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":"Molecular Mechanism of the Urate-lowering Effects of Calcium Channel Blockers","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Molecular Mechanism of the Urate-lowering Effects of Calcium Channel Blockers","subitem_title_language":"en"}]},"item_type_id":"2","owner":"3","path":["77"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-05-24"},"publish_date":"2017-05-24","publish_status":"0","recid":"1291","relation_version_is_last":true,"title":["Molecular Mechanism of the Urate-lowering Effects of Calcium Channel Blockers"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-06-20T16:02:30.227391+00:00"}