Cytochrome P-450 dependent monooxygenases in neuronal and glial cells: inducibility and specificity.
Distribution of the mixed function oxidases (MFO's) catalyzed by presence of multiple forms of cytochrome P-450 (P-450) was investigated in the neuronal and glial cells of the brain. The neuronal cells exhibited 2-3 fold higher activity of P-450 dependent arylhydrocarbon hydroxylase (AHH), 7-ethoxycoumarin-o-deethylase (ECOD) and 7-ethoxy-resorufn-o-deethylase (EROD) than the glial cells. Pretreatment with phenobarbital (PB) significantly increased (60-85%) the activity of ECOD in neuronal and glial cells, while a 140% increase was observed in neuronal AHH activity. Exposure to 3-methylcholanthrene (MC) resulted in a significant induction of the activity of AHH (102-345%), ECOD (115-150%) and EROD (75-120%) in the neuronal and glial cell preparations. The neurons, in general, exhibited greater sensitivity towards PB and MC induction. The present data indicate the differential sensitivity of these enzymes in neuronal and glial cells which could be used as a model to understand the selective action of certain neurotoxic agents.
Dhawan
A
A
Industrial Toxicology Research Centre, Lucknow, India.
Parmar
D
D
Das
M
M
Seth
P K
PK
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009457:Neuroglia / Q000201:enzymology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D010634:Phenobarbital