| Project/Area Number |
23590201
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平野 俊彦 東京薬科大学, 薬学部, 教授 (90173252)
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| Co-Investigator(Renkei-kenkyūsha) |
島津 元秀 (70124948)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ステロイド / 感受性 / カルシニューリン阻害薬 / ファーマコダイナミクス / 相互作用 / FKBP / タクロリムス / フォーマコダイナミクス / シクロスポリン / ステロイド感受性 / カルシニュリン阻害薬 / 薬力学的相互作用 / FKBP51 / FKBP52 / シクロフィリン40 |
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| Research Abstract |
The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which in turn binds to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. We examined the steroid sensitivity of mixed culture with both methylprednisolone (MPSL) and CNIs in 30 healthy subjects.and MPSL and cortisol sensitivity were examined before and after CNI administration in 23 renal transplant recipients.
Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroid can increase steroid sensitivity. However, we could not have demonstrated the action mechanism, though we are resolving the action mechanism, using Jurkat cell knockdown FKBP51 with SiRNA
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