| Project/Area Number |
16590467
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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, 医学部, 講師 (40140264)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hakuo Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (80094431)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | endogenous digitalis-like factor / bufadienolide / telocinobufagin / mass spectrometry / liquid chromatography / kidney / cardenolides / poisoning analysis / 内因性ジギタリス様物質 / ブファリン / マリノブフォトキシン / マリノブファギン / 血圧 / ELISA / モノクローナル抗体 / テロシノブフォトキシン / 副腎皮質 / 副腎髄質 / ブファジエノライド |
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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. Bufalin is a member of bufadienolide, and we recently found that this EDLF was in mammalian body fluid, especially in saliva. The tandem mass spectrometric signals of liquid chromatography-mass spectrometry (LC/MS) indicated that saliva bufalin is the same as authentic bufalin from toad. This study was opened in the international meeting of atherosclerosis. But due to the slight recovery of saliva, structural study was incomplete such as NMR.
During the above study, we found new bufadienolide, two-hydrogen added form of marinobufagin (MBG) that is telocinobufagin (TCB) in human plasma. This is the first report TCB in mammalian body fluid. Moreover, TCB in the plasma of chronic renal failure was co-existed with MBG and larger amount than MBG. This study indicated that metabolic and/or synthetic pathway may exist in mammalian bufadienolide.
In the cardenolide field, we found that Nanomolar level of ouabain increases intracellular calcium to produce nitric oxide in rat aortic endothelial cells.
The poisoning is also important problem in the clinical field of digitalis. We edited the series of toxicological analysis of drug and poisoning in the clinical laboratory
These strategy of studies become the important foundation stone of recent impressive finding of marinobufotoxin (MBT) in mouse adrenocortical cell line, Y-1, and hypertensive effect on the rat by continuously and small amount giving of MBT. This is the first study, which proves the existence in mammal and hypertensive effect of MBT. MBT becomes is new member of EDLF.
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