Suppression of clofibrate-induced peroxisome proliferation in rat liver by nicardipine, a calcium antagonist.
In vivo administration of nicardipine, nifedipine and diltiazem, known as calcium antagonists, suppressed the clofibrate-evoked 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.
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000037:antagonists & inhibitors; D042964:Acyl-CoA Dehydrogenase; D000818:Animals; D002332:Carnitine O-Acetyltransferase / Q000037:antagonists & inhibitors; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D002374:Catalase / Q000037:antagonists & inhibitors; D002994:Clofibrate / Q000494:pharmacology*; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors; D004110:Diltiazem / Q000494:pharmacology; D004746:Enoyl-CoA Hydratase / Q000037:antagonists & inhibitors; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000037:antagonists & inhibitors; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D009529:Nicardipine / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood
D004791:Enzyme Inhibitors; D014280:Triglycerides; D009529:Nicardipine; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002374:Catalase; D044943:Fatty Acid Desaturases; D042964:Acyl-CoA Dehydrogenase; D003605:D-Amino-Acid Oxidase; D002334:Carnitine O-Palmitoyltransferase; D002332:Carnitine O-Acetyltransferase; D004746:Enoyl-CoA Hydratase; D004110:Diltiazem; D002994:Clofibrate; D009543:Nifedipine