INTRACELLULAR CALCIUM ION-RELATED GENE EXPRESSION OF CYTOCHROMES P450
| Project/Area Number |
10672104
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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 |
Environmental pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
DEGAWA Masakuni UNIVERSITY OF SHIZUOKA, SCHOOL OF PHARMACEUTICAL SCIENCES PROFESSOR, 薬学部, 教授 (50134002)
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| Co-Investigator(Kenkyū-buntansha) |
NEMOTO Kiyomitsu UNIVERSITY OF SHIZUOKA, SCHOOL OF PHARMACEUTICAL SCIENCES RESEARCH ASSOCIATE, 薬学部, 助手 (90189366)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | CYTOCHROME P450 / CYP / GENE REGULATION / CALCIUM / CALCIUM CHANNEL BLOCKER / RAT / CULTURED HEPATOCYTE / LIVER / チトクロームP450 / CYPIA / CYP3A / CYP2E / 肝細胞 |
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| Research Abstract |
We have previously reported that calcium channel bockers such as nicardipine, verapamil and cinnarizine induce cytochromes P450 (CYP1A2, 3A1/3A2, 2B1/2B2 and 2E1) in the rat liver. In the present study, to determine whether all calcium channel blockers show the inductive activity for cytochromes P450 (CYP1A2, 3A1/3A2, 2B1/2B2 and 2E1), we first examined the induction of the CYPs in the rat liver by the metal ions, CoィイD12+ィエD1 and NiィイD12+ィエD1, which were characterized as calcium channel blockers, and found that these metal ions induced CYP1A2, while suppressed the gene expression of other CYPs. These suggest that the gene expression of CYPs with exception of CYP1A2 is not necessarily associated with intracellular calcium ion concentration. On the other hand, a cultured hepatic cell line is thought to be a useful tool for investigating the mechanism of gene expression of CYPs because there is a heterogeneity in liver cells. Therefore, we examined the gene expression of CYPs by RT-PCR using the cell line, which was previously established from male SD rat liver, and the results suggest that the gene expression of CYPs, especially CYP2B2 and 3A1/2, is mainly regulated by cytoplasmic suppressive factor(s) rather than by intracellular calcium ion.
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Report
(3 results)
Research Products
(1 results)
