Rabbit Liver and Lung Microsomal Metabolism of $\beta$-Nicotyrine:Isozyme Specificities toward the Oxidation of $\beta$-Nicotyrine

Rabbit Liver and Lung Microsomal Metabolism of $\beta$-Nicotyrine:Isozyme Specificities toward the Oxidation of $\beta$-Nicotyrine

Studies on the biodisposition of beta-nicotyrine by lung and liver microsomes was examined in order to provide a better understanding of its fate in this tissue. beta-nicotyrine (100$\mu$M) was incubated with microsomes (1 mg/ml) prepared from New Zealand White rabbits. The rate of oxidation observed in lung microsomal incubations was 1.7 nmoles $\beta$-nicotyrine oxidized mg$^{-1}$ min$^{-1}$ compared with 2.7 nmoles $\beta$-nicotyrine oxidized mg$^{-1}$ 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 $\beta$-nicotyrine oxidized nmole cytochrome P-450$^{-1}$ min$^{-1}$) was approxiamtely 4 times greater than liver microsomes (2.3 nmoles $\beta$-nicotyrine oxidized nmole cytochrome P-450$^{-1}$ min$^{-1}$). Isozyme studies on the oxidation of $\beta$-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 $\alpa$-methyl ABT, metabolic inhibitor(MI) complex formation. The results of this inhibition study would appear to indicate the $\beta$-nicotyrine is metabolized predominantly by pulmonary isozyme 5.