Abstract

• 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.