Effect of ethanol on cytochrome P450 in the rat brain.
After a single dose of ethanol (0.8 ml/kg) administered intraperitoneally, the P450 content of the rat brain increased from 62 +/- 19 to 230 +/- 97 pmol/g (wet weight) of tissue (mean +/- SD, n = 5). Most of this increase could be accounted for by a 10- to 20-fold increase in the olfactory lobes and hypothalamic preoptic area. The P450s were identified by Western blot analysis and by microsequencing of the N-terminal ends after resolution of the proteins on SDS gels. They were identified as P450 2C7, 2C11, 2E1, 4A3, 4A8, and a member of the P450 2D family. In P450 extracted from the brains of control rats, P450 2C and 4A were also detectable but at a much lower concentration. P450 1A1, 2A1, 2B1, or 3A was not detected in the brains of either control or ethanol-treated rats. Oral administration of the same dose of ethanol resulted in a similar increase in the whole brain but smaller effects in the olfactory lobes. This effect of ethanol on the P450 in the brain has implications for the mechanism of toxicity and the development of tolerance to ethanol and for the effects of other drugs and environmental pollutants that act on the central nervous system.
Warner
M
M
Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden.
Gustafsson
J A
JA
D000079:Acetaldehyde / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D000079:Acetaldehyde