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(CYP1A2，3A1/3A2，2B1/2B2 and2E1)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 and2E1)，we first examined the induction of the CYPs in the rat liver by the metal ions，Co I D12文件D1 and Ni I D 12 I D 1，which were characterized as calcium channel blockers，and found that these metal ions induced CYP 1 A 2，while supped gene the pothion ofThese suggest that the gene expression of CYPs with exception of CYP1A2is 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。

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.