Differential effect of chronic nicotine administration on brain cytochrome P4501A1/2 and P4502E1.
The effects of chronic nicotine administration on the enzymatic activities and immunoreactivities of P4501A1/2 and P4502E1 were determined in microsomal fractions from brain regions and liver. Chronic nicotine increased 7-ethoxyresorufin O-deethylase activity and P4501A1/2 immunoreactivity in hippocampus and brain stem, decreased values in cerebral cortex, thalamus, and striatum, and did not affect parameters in other brain regions. In contrast, N-nitrosodimethylamine N-demethylase activity from nicotine-injected rats increased in all brain regions examined, and this increase was associated with increased P4502E1 immunoreactivity. Chronic nicotine did not alter either enzyme activities or immunoreactivities of these isoforms in hepatic microsomes.
Anandatheerthavarada
H K
HK
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa 33612.
Williams
J F
JF
Wecker
L
L
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism*; D004334:Drug Administration Schedule; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D008970:Molecular Weight; D009538:Nicotine / Q000494:pharmacology*; D009928:Organ Specificity; D010088:Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D010089:Oxidoreductases, N-Demethylating