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KMID : 0043319910140020130
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Archives of Pharmacal Research
1991 Volume.14 No. 2 p.130 ~ p.136
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Role of Cytochrome P-450 in the Bioactivation of Nicotine
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Kim BH
Trevor A
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Abstract
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Nicotine (100mcM) was incubated with microsomes (1mg/ml) prepared from New Zealand White rabbits. On the basis of microsomal weight the rate of nicotine oxidation was slightly slower in lung compared to liver. However, when the rates of nicotine oxidation were calculated on the basis of cytochrome P-450 concentration, the specific activity of the metabolic oxidation catalyzed by lung was approximately 4 times greater than liver (6.4 vs 1.65nmoles nicotine oxidized. nmole cytochrome P-450-1 min-1). These studies employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme 2 and 6 specific inhibitor alpha-methylbenzyl ABT, metabolite inhibitors, norbenzphetamine and N-hydroxyamphetamine, TCDD induction and Arochlor 1260 pretreatment. These results support the conclusion that nicotine metabolism by rabbit lung microsomes is mediated primarily by cytochrome P-450 isozyme 2.
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