Qualitative Alteration in Hepatic Microsomal Cytochrome P450 Apoproteins Associated with Bile Duct Ligation, and the Administration of Cholic Acid and Phenobarbital

We have investigated in rat liver whether different forms of cytochrome P-450 are alterated in hepatic disorders associated with impaired drug metabolism. Total hepatic cytochrome P-450 is decreased after either bile duct ligation or the administration of estradiol. In contrast, phenobarbital administrated alone increase hepatic content of cytochrome P-450, and when administrated with estradiol the reduction in cytochrome P-450 was prevented. Four forms of microsomal cytochrome P-450 apoproteins, ranging in molecular weight from 50 000 to 58,000, were tentatively identified in a sodium dodecyl sulfate(SDS)-6M urea polyaocrylamide gel electrophoresis system. Phenobrbital administration icreased primarily band IV(50,000 daltons). Bile duct ilgation was associated with a marked reduction in bands II and III while bands II and III were decreased with estradiol benzoate administration. Sumultaneous administration of phenobarbital and estradiol demonstrated a return of band I and an increase in density of bands III and IV. Simultaneous administration of cholic acid and estradiol demonstrated a return of band I and not altered in band III and IV. These studies support the hypothesis that multiple forms of cytochrome P-450 are present in liver microsomal membranes and that alterations in spenific apoproteins may be associated with an increase or a decrease in the functional properties of cytochrome P-450.