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  1. Dokkyo Journal of Medical Sciences
  2. 43(1) 2016

Molecular Mechanism of the Urate-lowering Effects of Calcium Channel Blockers

https://dmu.repo.nii.ac.jp/records/1291
https://dmu.repo.nii.ac.jp/records/1291
4642d7e5-d2bb-409b-97d4-9c3996eae88f
名前 / ファイル ライセンス アクション
KJ00010141602.pdf KJ00010141602.pdf (310.4 kB)
Item type [ELS]学術雑誌論文 / Journal Article(1)
公開日 2017-05-24
タイトル
タイトル Molecular Mechanism of the Urate-lowering Effects of Calcium Channel Blockers
言語 en
言語
言語 eng
キーワード
言語 en
主題 Calcium Channel Blockers
キーワード
言語 en
主題 Uricosuric Drugs
キーワード
言語 en
主題 Urate
キーワード
言語 en
主題 Transporters
キーワード
言語 en
主題 Urat1
キーワード
言語 en
主題 Xanthine Oxidase
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
雑誌書誌ID
収録物識別子 AA00629581
論文名よみ
タイトル Molecular Mechanism of the Urate-lowering Effects of Calcium Channel Blockers
著者 Tsuchiya, Go

× Tsuchiya, Go

en Tsuchiya, Go

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Hori, Takayuki

× Hori, Takayuki

en Hori, Takayuki

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Onizawa, Nobuyuki

× Onizawa, Nobuyuki

en Onizawa, Nobuyuki

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Otani, Naoyuki

× Otani, Naoyuki

en Otani, Naoyuki

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Tanaka-nakadate, Sawako

× Tanaka-nakadate, Sawako

en Tanaka-nakadate, Sawako

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Iseki, Tatou

× Iseki, Tatou

en Iseki, Tatou

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Ouchi, Motoshi

× Ouchi, Motoshi

en Ouchi, Motoshi

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Hayashi, Keitaro

× Hayashi, Keitaro

en Hayashi, Keitaro

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Jutabha, Promsuk

× Jutabha, Promsuk

en Jutabha, Promsuk

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Oba, Toru

× Oba, Toru

en Oba, Toru

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Fukuda, Hirotsugu

× Fukuda, Hirotsugu

en Fukuda, Hirotsugu

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Anzai, Naohiko

× Anzai, Naohiko

en Anzai, Naohiko

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著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Material And Environmental Chemistry, Graduate School Of Engineering, Utsunomiya Niversity:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
著者所属(英)
en
Department Of Pharmacology And Toxicology, Dokkyo Medical University School Of Medicine:Department Of Cardiac And Vascular Surgery, Dokkyo Medical University School Of Medicine
記事種別(英)
内容記述タイプ Other
内容記述 Original
抄録(英)
内容記述タイプ Other
内容記述 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.
書誌情報 Dokkyo journal of medical sciences

巻 43, 号 1, p. 23-29, 発行日 2016-03-25
ISSN
収録物識別子タイプ ISSN
収録物識別子 03855023
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