| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
|---|
| 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.
|
