| Project/Area Number |
18590543
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
KOMIYAMA Yutaka Kansai Medical University, Faculty of Medicine, Assistant professor (40140264)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hakuo Kansai Medical University, Faculty of Medicine, Professor (80094431)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | endogenous digitalis-like factor / bufadienolide / cardenolides / marinobufotoxin / renin / angiotensin / esterase / cardiotonic steroid / コレステロールエステラーゼ / 質量分析 / 組織カリクレイン / ショック / 腎臓 / 腎尿細管 |
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| Research Abstract |
Endogenous digitalis-like factor (EDLF) act as important modulator for water and salt metabolism. From recent studies endogenous digitalis-like factor is consisted of cardenolides and bufadienolides. Recently we found marinobufotoxin (MBT) as the new member of EDLF. The structure of this compound was confirmed by tandem mass spectrometric signals of liquid chromatography-mass spectrometry and nuclear magnetic resonance (NMR) analysis. Interestingly this compound consists of cardiotonic steroid with C6-chain and amino acids, argentine. And the esterase for this side chain was searched. The reaction of this esterase mimicked by the tissue kallikrein and other esterases such as cholesterol esterase were relatively slow and the physiological meanings are still ambiguous. But we found the contribution of rennin-angiotensin system (RAS) and MBT on hypertension with use of SHR rats. In the angiotensin-receptor blocker (ARB), telmisartan group, the plasma level of MBT was lower than that in the control group. The urine MBT excretion increase after 2 and 4 weeks but the MBT excretion modified by the ARB did not increase and the blood pressure did not increase. These results suggested that MBT contributed the control mechanism in SHR with RAS. And this analytic system was also applied to clinical toxicology area.
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