Cytochrome P450 (P450) isoenzyme specific dealkylation of alkoxyresorufins in rat brain microsomes.

摘要: Characterization of xenobiotic metabolizing cytochrome P450s (P450s) was carried out in rat brain microsomes using the specific substrates, 7-pentoxy- and 7-ethoxyresorufin (PR ER), metabolized liver by P450 2B1/2B2 1A1/1A2 respectively 7-benzyloxyresorufin (BR), a substrate for both isoenzymes. Brain catalysed O-dealkylation PR, BR ER presence NADPH. The ability to dealkylate alkoxyresorufins varied different regions brain. Microsomes from olfactory lobes exhibited maximum pentoxyresorufin-O-dealkylase (PROD), benzyloxyresorufin-O-dealkylase (BROD) ethoxyresorufin-O-dealkylase (EROD) activities. dealkylation found be inducer selective. While pretreatment with phenobarbital (PB; 80 mg/kg; i.p. × 5 days) resulted significant induction PROD (3-4 fold) BROD (4-5 activities, 3-methylcholanthrene (MC; 30 had no effect on activity only slight that (1.4 fold). MC significantly induced EROD (3 while PB it. Kinetic studies have shown this increase activities following inducers associated velocity reaction (Vmax) O-dealkylation. In vitro organic inhibitors antibodies further provided evidence is isoenzyme specific. addition a-naphthoflavone (ANF), an inhibitor reactions antibody hepatic isoenzymes produced concentration-dependent inhibition activity, metyrapone, inhibited vitro. data suggest that, as case liver, can used biochemical tool characterise metabolising selectivity microsomes.