Interaction of 9-hydroxyellipticine with two forms of partially purified rabbit lung cytochrome P-450. Inhibition of lung microsomal benzo[a]pyrene hydroxylase.
9-Hydroxyellipticine (9-OHE), a potent inhibitor of rat liver monooxygenase activities, binds to the various forms of partially purified lung cytochromes P-450 from untreated and 3-methylcholanthrene (3-MC)-treated rabbits. The spectral data (lambda max: 428 nm (ox.), 447 nm (red.), Ks: 10 microM and 5 muM for cytochrome I and cytochrome II from 3-MC-treated rabbits respectively) resemble those obtained with cytochrome P-450 purified from liver of Aroclor 1254-pretreated rats (lambda max: 428 nm (ox.), 445 nm (red.), Ks: 8 microM). 9-OHE has been shown to inhibit the benzo[a]pyrene hydroxylase activity of rat and rabbit lung microsomes. The inhibitory effect was higher towards the 3-MC-induced lung microsomes than with the control microsomes. However, the lung microsomes, as well as the liver microsomes of rabbits were less sensitive to inhibition by 9-OHE than the corresponding microsomes from rats. These results suggest that rabbit and rat cytochromes P-450 have subtle structural differences.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001579:Benzopyrene Hydroxylase / Q000037:antagonists & inhibitors*; D002417:Cattle; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004611:Ellipticines / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D011817:Rabbits; D051381:Rats
D000470:Alkaloids; D004611:Ellipticines; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; C008009:9-hydroxyellipticine; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases