INTRACELLULAR CALCIUM ION-RELATED GENE EXPRESSION OF CYTOCHROMES P450

We have previously reported that calcium channel bockers such as nicardipine， verapamil and cinnarizine induce cytochromes P450 （CYP1A2，3 A1/3 A2，2 B1/2 B2 and 2 E1） in the rat liver。在目前的研究中，确定所有钙通道阻断器显示细胞色素P450的诱导活动。（CYP1A2，3 A1/3 A2，2 B12 B2 and 2 E1）， we first examined the induction of the CYPs in the rat liver by the metal ions，Coy D12+ y D1 and Ni y D12+ y D1， which were·terized as calcium channel blockers，并发现这些金属诱导CYP 1A 2，但当其他CYPs的基因表达时，它们被抑制了。这些建议是，CYPs的基因表达与CYP 1A 2例外不一定与内钙离子浓缩有关。在另一方面，一种文化的肝炎细胞线是一种有用的工具，用于研究CYPs基因表达的机制，因为它是肝脏细胞中的一种异质性。因此，我们通过RT-PCR测试了CYPs使用细胞线进行的基因表达，以前从男性SD大鼠liver中确定了基因表达，并提出了关于CYPs基因表达的结果，特别是CYP 2B 2和3A 1/2，主要是由细胞系抑制因子（s）不如由内源钙离子体调节。

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.