LOCALIZATION AND CHARACTERIZATION OF CYTOCHROME-P450 IN THE BRAIN - IN-VIVO AND IN-VITRO INVESTIGATIONS ON PHENYTOIN-INDUCIBLE AND PHENOBARBITAL-INDUCIBLE ISOFORMS

The antiepileptic drug phenytoin is known to be substrate as well as i nducer of cytochrome P450 (P450) in the mammalian liver. We were able to show the expression of P450 species immunorelated to the main pheny toin-induced hepatic isoforms in mice (CYP2C29) and rats (CYP2B1,2) al so in the central and peripheral nervous system and primary cultures o f cell types from the brain. The 2B1,2 related protein showed only a w eak constitutive expression in vivo and in vitro analyzed by immunocyt ochemistry, in situ hybridization, Northern blot and RT/polymerase cha in reaction (PCR). Contrary, the CYP2C29 related form is inducible by phenytoin at about 1.5-fold starting from an already higher constituti ve level. This protein is characterized by a remarkable tendency to di ssociate from the endomembranes during tissue homogenization. The supe rnatant of microsomal pellet is able to metabolize phenytoin in a reco nstitutive system.