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Structural analysis of endogenous digitalis and studies on the role of it in electrolytes and blood pressure control. In particular, studies on a novel substance, marinobufagenin with double hydrogen.

Research Project

Project/Area Number 14572191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionKansai Medical University

Principal Investigator

TAKAHASHI Hakuo  Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (80094431)

Co-Investigator(Kenkyū-buntansha) KOMIYAMA Yutaka  Kansai Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (40140264)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsendogenous digitalis / marinobufagenin / telocinobufagin / sodium loading / liquid chromatography / mass spectrometry / ELISA / 慢性腎不全 / 液体クロマトグララフィー / 構造解析
Research Abstract

Inhibition of sodium-potassium adenosine triphosphatase (Na,K-ATPase) by marinobufagenin (MBG) or telocinobufagin (TCB) are more potent than that of ouabain. We found that those bufadienolides are circulating in human blood, upon analyzing the structure by using multiple steps of liquid chromatography (LC) and mass-spectrometry (LC/MS), nuclear magnetic resonance (NMR). TCB has two more hydrogen than MBG.Plasma concentration of TCB was almost double of MBG, the correlation among them was highly significant. Therefore, we thought that the TCB is hydrolysed to MBG.Since the concentration of TCB is much higher than MBG, TCB was thought to be the cardinal endogenous digitalis. This is the first report to show the existence of TCB in mammalian samples. Furthermore, the concentration was compared in normal subjects and patients with terminal renal failure, and it was almost twice higher in the patient plasma as compared to it in normal subjects. Therefore, both TCB and MBG may be functioning as the physiological regulator of electrolytes and consequently blood pressure.
Then, we made monoclonal antibody for TCB, but unfortunately it cross-reacted with MBG too, and enzyme-linked immunosorbent assay (ELISA) was developed. Because this ELISA system was interfered with constituents of plasma, it was useful only for measurement of urine samples. By using this ELISA, effects of sodium-loading was tested in rats, we found that rats with high salt diet excreted more TCB/MBG than in rats with normal diet.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (26 results)

All 2005 2004 2003 2002 Other

All Journal Article (13 results) Book (1 results) Publications (12 results)

  • [Journal Article] A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure.2005

    • Author(s)
      Komiyama, Takashi et al.
    • Journal Title

      Clinical Biochemistry 38

      Pages: 36-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure.2005

    • Author(s)
      Komiyama Y, Dong XH, Nishimura N, Masaki H, Yoshika M, Masuda M, Takahashi H
    • Journal Title

      Clin Biochem. 38(1)

      Pages: 36-45

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Nanomoler level of ouabain increases intracellular calcium to produce nitric oxide in rat aortic endothelial cells2004

    • Author(s)
      Dong, Takahashi et al.
    • Journal Title

      Clinical and Experimental Pharmacology and Physiology 31

      Pages: 276-283

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Haemoglobin level influences plasma brain natriuretic peptide concentration.2004

    • Author(s)
      Tsuji, Takahashi, et al.
    • Journal Title

      Acta Cardiology 59

      Pages: 527-531

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Association between cardiovascular autonomic neuropathy and left ventricular hypertrophy in diabetic haemodialysis patients.2004

    • Author(s)
      Nishimura M, Hashimoto T, Kobayashi H, Fukuda T, Okino K, Yamamoto N, Nakamura N, Yoshikawa T, Takahahsi H
    • Journal Title

      Nephrol Dial Transplant 19

      Pages: 2532-2538

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] High-performance liquid chromatographic method with column-switching and post-column reaction for determination of serotonin levels in platelet-poor plasma.2004

    • Author(s)
      Hirowatari Y, Hara K, Kamihata H, Iwasaka T, Takahashi H
    • Journal Title

      Clin Biochem (2004) 37

      Pages: 191-197

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The ratio of plasma to Whole-blood serotonin may be a novel marker of atherosclerotic cardiovascular disease.2004

    • Author(s)
      Hara K, Hirowatari Y, Yoshika M, Komiyama Y, Tsuka Y, Takahashi H
    • Journal Title

      J Lab Clin Med (2004)

      Pages: 31-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Nanomolar level of ouabain increases intracellular calcium to produce nitric oxide in rat aortic endothelial cells.2004

    • Author(s)
      Dong XH, komiyama Y, Nishimura N, Masuda M, Takahashi T
    • Journal Title

      Clin and Exp Pharmacol and Physiol (2004) 31(5-6)

      Pages: 276-283

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Haemoglobin level influences plasma brain natriuretic peptide concentration.2004

    • Author(s)
      Tsuji H, Nishino N, Kimura Y, Yamada K, Nukui M, Yamamoto S, Iwasaka T, Takahashi H.
    • Journal Title

      Acta Cardiol. 59(5)

      Pages: 527-531

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Measurement of soluble Fcγ receptor type IIIa dervied from macrophages in plasma : increase in patients with rheumatoid arthritis.2003

    • Author(s)
      Masuda, Takashi, et al.
    • Journal Title

      Clinical Experimental Immunology 132

      Pages: 477-484

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Different remodeling against left ventricular overload between diabetic and non-diabetic haemodialysis patients.2003

    • Author(s)
      Nishimura, Takahashi, et al.
    • Journal Title

      Clinical and Experimental Pharmacology and Physiology 30

      Pages: 786-792

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Possible involvement of TNF-a in left ventricular remodeling in hemodialysis patients.2003

    • Author(s)
      Nishimura, Takahashi, et al.
    • Journal Title

      Journal of Nephrology 16

      Pages: 641-649

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Increase of soluble Fc gamma RIIIa derived from macrophages in plasma from patients with atherosclerosis2002

    • Author(s)
      Masuda M, Takahashi H.
    • Journal Title

      Rinsho Byori. 50(5)

      Pages: 502-505

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Book] 「早朝高血圧の治療」虚血性心疾患を伴った場合2003

    • Author(s)
      高橋伯夫
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Dong, Takahashi et al.: "Nanomoler level of ouabain increases intracellular calcium to produce nitric oxide in rat aortic endothelial cells."Clinical and Experimental Pharmacology and Physiology. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masuda, Takahashi, et al.: "Measurement of soluble Fcγ receptor type IIIa derived from macrophages in plasma : increase in patients with rheumatoid arthritis."Clinical and Experimental Immunology. 132. 477-484 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishimura, Takahashi, et al.: "Different remodelling against left ventricular overload between diabetic and non-diabetic haemoclialysis patients."Clinical and Experimental Pharmacology and Physiology. 30. 786-792 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishimura, Takahashi, et al.: "Possible involvement of TNF-α in left ventricular remodeling in hemodialysis patients"Journal of Nephrology. 16. 641-649 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 高橋伯夫: "粥状動脈硬化の評価のための新しい臨床化学検査"臨床化学. 32(1). 35-41 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 高橋伯夫: "「早朝高血圧の治療」虚血性心疾患を伴った場合"総合医学社. 114 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi H, et al.: "Effect of vasodilatory beta-adrenoceptor blockers on cardiovascular haemodynamics in anaesthetized rats"Clinical and Experimental Pharmacology and Physiology. 29(3). 198-203 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taniuchi S, Takahashi H. et al.: "Differential diagnosis and clinical course of autoimmune neutropenia in infancy : comparison with congenital neutropenia"Acta Paedatrics. 91. 1179-1182 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋伯夫: "高感度CRP測定法の病態診断的有用性"日本医事新報. 4079. 85 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋伯夫: "CRP測定法と臨床的意義の再評価(4) 高感度免疫測定法がもたらす新たな病態診断的有用性 -CRPを中心に-"臨床病理. 50(1). 30-39 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋伯夫: "臨床高血圧"朝倉書店. 4 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋伯夫: "高血圧研究の歴史"先端医学社. 16 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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