Immunohistochemical demonstration of ethanol-inducible P450 2E1 in rat brain.
The microsomal ethanol-oxidizing system (MEOS) is a P450-dependent pathway for ethanol oxidation in hepatic microsomes. The bulk of MEOS activity is catalyzed by P450 2E1 (an ethanol-inducible isozyme of P450) in animal livers treated with ethanol. Rat brains also metabolize certain drugs, and it is theorized that a mechanism for drug metabolism exists within the brain which acts on P450. We compared immunohistochemical localization of P450 2E1 between ethanol-treated rats and pair-fed control rats. In control rats, immunoreactive P450 2E1 was detected in minute amounts in both basal ganglia and cerebellar cortices. After ethanol treatment, the content of P450 2E1 increased in the basal ganglia, and the enzyme was also induced in the cerebellar cortices, substantia nigra and hippocampus. We speculate that the rat brain metabolizes ethanol by P450 2E1.
Sohda
T
T
First Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Shimizu
M
M
Kamimura
S
S
Okumura
M
M
D000437:Alcoholism / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics*; D007124:Immunoenzyme Techniques; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating