| Project/Area Number |
12672225
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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 |
応用薬理学・医療系薬学
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| Research Institution | Tokyo University of Pharmacy and life Science |
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Principal Investigator |
KASUYA Yasuji Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor, 薬学部, 教授 (90096686)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBASAKI Hiromi Tokyo University of Pharmacy and Life Science, School of Pharmacy, Assistant Professor, 薬学部, 講師 (20206121)
FURUTA Takashi Tokyo University of Pharmacy and Life Science, School of Pharmacy, Associate Professor, 薬学部, 助教授 (70120152)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | cortisol / cortisone / stable isotope methodology / 11β-HSD activity / hypertension / GC-MS-SIM / 13C_4-and 2H_1-label / pharmacokinetic analysis / 安定同位体標識 / 11β-HSD2酵素活性評価 / GC-MS分析 |
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| Research Abstract |
This study is concerned with oral administrations of [1,2,4,19-13C_4] cortisol (cortisol-13C_4) and [1,2,4,19-13C_4,11α-^2H] cortisol (cortisol-13C_4,^2H_1) to a human subject to reliably evaluate the individual activities of two isozymes of 11β-HSD. The use of a GC-MS method allowed the simultaneous measurement of the plasma concentrations of cortisol-13C_4, ^2H_1, cortisone-13C_4, and cortisol-13C_4 together with endogenous cortisol and cortisone. The lossof 11α-^2H during the conversion of cortisol-13C_4, ^2H_1 to cortisone-13C_4 by 11β-HSD2 and the regenerated cortisol-13C_4 from cortisone-13C_4 by 11β-HSD1 provided a direct and accurate means of distinguishing the activities of the two isozymes. The kinetic analysis associated with the metabolism of orally administered cortisol-13C_4 and cortisol-13C_4, ^2H1 was of great importance in assessing the 11β-HSD activities.
This stable isotope approach offered unique advantages since it allowed to measure stable isotopically labeled cortisol and its labeled metabolite cortisone simultaneously with endogenous (unlabeled) cortisol and cortisone. Very important was the potential use of stable isotopically labeled cortisol in man as a tracer for the native cortisol to recognize the conversion of cortisol to cortisone in the kidney. Our results from the stable isotope methodology strongly suggest that cortisol-13C_4, ^2H_1 used in this study served as an appropriate tracer for elucidating the kinetics of the interconversion of cortisol to cortisone in man.
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