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KMID : 0614019890050010037
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Journal of Pharmaceutical Sciences (C.N.U.)
1989 Volume.5 No. 1 p.37 ~ p.46
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Rabbit Liver and Lung Microsomal Metabolism of β-Nicotyrine:Isozyme Specificities toward the Oxidation of β-Nicotyrine
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Kim Bong H.
Shigenaga M.K.
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Abstract
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Studies on the biodisposition of β-nicotyrine by lung and liver microsomes was examined in order to provide a better understanding of its fate in this tissue. β-nicotyrine (100 μM) was incubated with microsomes (1 ㎎/㎖) prepared from New Zealand White rabbits. The rate of oxidation observed in lung microsomal incubations was 1.7 nmoles β-nicotyrine oxidized ㎎^-1 min^-1 compared with 2.7 nmoles β-nicotyrine oxidized ㎎^-1 min^-1 by the liver microsomal preparation. However, when these rates were expressed as a function of cytochrome P-450 content, the specific activity of the metabolic oxidation catalyzed by lung (8.3 nmoles β-nicotyrine oxidized nmole cytochrome P-450^-1 min^-1) was approxiamtely 4 times greater than liver microsomes (2.3 nmoles β-micotyrine oxidized nmole cytochrome P-450^-1 min^-1). Isozyme studies on the oxidation of β-nicotyrine employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme 2 and 6 specific inhibitor α-methyl ABT, metabolic inhibitor (MI) complex formation. The results of this inhibition study would appear to indicate the β-nicotyrine is metabolized predominantly by pulmonary isozyme 5.
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