Suppression of clofibrate‐induced peroxisome proliferation in rat liver by nicardipine, a calcium antagonist

FEBS Letters

Suga, Tetsuya¹  Watanabe, Takafumi¹ 

[1]Department of Clinical Biochemistry, Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo, Japan

关键词: Nicardipine;    Nifedipine;    Diltiazem;    Enzyme inhibition;    Peroxisome proliferation;    DAAO;    D-amino acid oxidase;    FAOS;    cyanide-insensitive fatty acyl-CoA oxidizing system;    FADH;    fatty acyl-CoA dehydrogenase;    CAT;    carnitine acetyltransferase;    CPT;    carnitine palmitoyltransferase;   

DOI  :  10.1016/0014-5793(88)80756-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In vivo administration of nicardipine, nifedipine and diltiazem, known as calcium antagonists, suppressed the clofibrateevoked induction of activities of peroxisomal enzymes, such as the peroxisomal fatty acyl-CoA oxidizing system and carnitine acetyltransferase. The inhibition activity of nicardipine with respect to clofibrate induction of the two enzyme systems was 62 and 33%, respectively. Induction of the peroxisomal bifunctional protein, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, by clofibrate was suppressed about 60% by nicardipine on analysis of the hepatic protein composition by SDS-polyacrylamide gel electrophoresis. Other drugs also exhibited similar inhibitory activity. These results provide the first demonstration of calcium antagonists, e.g. nicardipine, nifedipine and diltiazem, acting as inhibitors of peroxisome proliferation in animals. Such drugs might become useful as tools for elucidating the mechanism of peroxisome proliferation and for determination of the pathological conditions under which peroxisomal function is impaired.

【 授权许可】

Unknown