2011 Fiscal Year Final Research Report
A new study of enzyme induction involved in pharmacokinetic : Identification of molecular mechanism for a novel enzyme induction
| Project/Area Number |
21590173
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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 |
Medical pharmacy
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| Research Institution | Tohoku Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | MRP3 / 酵素誘導 / 転写因子 / 核内レセプター / CYP3A4 |
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| Research Abstract |
Drug metabolizing enzyme CYP3A4 and excretory transporter MRP3 are induced by same compounds, being predicted the existence of similar molecular mechanism in both induction. CYP3A4 and MRP3 were strongly induced by treatment with clotrimazole and aryl hydrocarbon receptor(AhR) ligands such as polycyclic aromatic hydrocarbons. Those compounds induced CYP3A4 through activation of pregnane X receptor(PXR) but not through activation of AhR. On the other hand, MRP3 induction was not involved in AhR activation, although a region including a nucleotide sequence similar to AhR binding cis-element was found in an enhancer region(-6.8Kb). Together with these results, CYP3A4 is predominantly induced through activation of PXR and MRP3 seems to be induced through a novel gene transcription involving no receptor previously reported.
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[Presentation] 板藍根によるCYP3A4活性誘導の検討2011
Author(s)
Sugawara R, Kumagai T, Miura M, Takahashi S, Sasaki T, Sakaguchi S, Miyairi S, Nagata K
Organizer
第50回日本薬学会東北支部大会
Place of Presentation
仙台
Year and Date
2011-10-29
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