| Project/Area Number |
62570382
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
ATSUO Goto Second Department of Internal Medicine Faculty of Medicine, University of Tokyo, 医学部(病), 助手 (00150277)
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| Co-Investigator(Kenkyū-buntansha) |
KAORU Yamada Second Department of Internal Medicine Faculty of Medicine, University of Tokyo, 医学部(病), 医員 (00735152)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1988: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Endogenous digitalis-like factor / Ouabain / Vascular smooth muscle cells / Na^+-K^+-ATPase inhibitor Renal tubular epithelial cells / Salt and hypertension / essential hypertension / Na^+、K^+-ATPase抑制因子 / Na利尿ホルモン / 本態性高血圧症 / Na^+, K^+-ATPase抑制因子 |
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| Research Abstract |
Endogenous digitalis-like factor, which is supposedly the natural ligand of the digitalis receptor of the NA^+,K^+-ATPase, has long been postulated to exist in the mammalian body.Such a factor may act as a specific regulator of the sodium pump and play important roles in the regulation of sodium excretion and the pathogenesis of human essential hypertension. Despite many worldwide attempts to elucidate the precise nature of this digitalis-like factor, it had eluded purification and definite characterization.
We have recently found that an inhibitory effect on [^3H]ouabain binding to intact human erythrocytes is the most sensitive and relatively specific method to determine digitalis-like activity. We were able to purify a polar digitais-like factor from human urine based on this assay system. This compound, a competitive and reversibel inhibitor, closely resembles ouabain in its polarity, molecular weight, non-peptidic nature and mode of action except for its UV absorption spectrum. This digitalis-like factor shared many biological activities of ouabain and was capable of acting on intact vascular smooth muscle cells and renal tubular epithelial cells. This compound increased cytosolic free calcium concentration in cultured vascular smooth muscle cells and augmented tension in rabbit aorta. Furthermore, this factor induced moderate natriuresis in bioassay rats.
These observations strongly suggest that the polar digitalis-like factor we isolated from human urine may be the long-sought digitalis-like agent, a modulator of vascular tone and a regulator of sodium excretion. Whether this compound is causally related to human essential hypertension remains to be clarified.
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