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2003 Fiscal Year Final Research Report Summary

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
Keywordsendogenous digitalis / marinobufagenin / telocinobufagin / sodium loading / liquid chromatography / mass spectrometry / ELISA
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.

  • Research Products

    (14 results)

All 2005 2004 2003 2002

All Journal Article (13 results) Book (1 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
    • Total Pages
      28-29
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2006-07-11  

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