Cytochrome P450-dependent alkoxyphenoxazone dealkylase activities in lung microsomes from untreated and beta-naphthoflavone-treated rats: effect of in vitro inhibitors

The reactivities of four alkoxyphenoxazone derivatives toward cytochrome P450-dependent monooxygenase activity were studied in lung microsomes from control and beta-naphthoflavone (BNF)-treated rats. Ethoxyphenoxazone (EtOPh)- and methoxyphenoxazone (MeOPh)-dealkylases were induced by beta NF (16- a...

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Bibliographic Details
Published inResearch communications in chemical pathology and pharmacology Vol. 57; no. 3; p. 375
Main Authors Rabovsky, J, Judy, D J
Format Journal Article
LanguageEnglish
Published United States 01.09.1987
Subjects
Animals
Benzoflavones - pharmacology
beta-Naphthoflavone
Cytochrome P-450 CYP1A1
Cytochrome P-450 Enzyme System - physiology
Dealkylation
Flavonoids - pharmacology
In Vitro Techniques
Lung - enzymology
Male
Metyrapone - pharmacology
Microsomes - enzymology
Oxidoreductases - antagonists & inhibitors
Oxidoreductases - metabolism
Rats
Rats, Inbred Strains
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Summary:The reactivities of four alkoxyphenoxazone derivatives toward cytochrome P450-dependent monooxygenase activity were studied in lung microsomes from control and beta-naphthoflavone (BNF)-treated rats. Ethoxyphenoxazone (EtOPh)- and methoxyphenoxazone (MeOPh)-dealkylases were induced by beta NF (16- and 3.9-fold respectively), whereas benzyloxyphenoxazone (BzOPh)- and pentoxyphenoxazone (PeOPh)-dealkylase activities were unchanged after pre-treatment with beta NF. The specific activities of BzOPh'ase from control- and beta NF-treated rats and EtOPh'ase from beta NF-treated rats were sufficiently high (214-560 pmoles resorufin per min per mg protein) for routine biochemical studies. Each differed in its sensitivity toward the in vitro inhibitors, alpha-naphthoflavone (ANF) and metyrapone (MP). In lung microsomes from beta NF-treated rats the I50 (MP) = 7.6 X 10(-5) M for EtOPh'ase and 1.0 X 10(-6) M for BzOPh'ase. I50 (ANF) = 3.8 X 10(-8) M for EtOPh'ase. I50 (ANF) for BzOPh'ase could not be determined; at the highest concentration of ANF (10(-3) M), 50% inhibition was not observed. The presence of high levels of two distinct forms of lung microsomal P450-dependent alkoxyphenoxazone dealkylases, BzOPh'ase from untreated and beta NF-treated rats and EtOPh'ase from beta NF-treated rats, will be useful for studies on specific P450-xenobiotic interactions in rat pulmonary tissue.
ISSN:0034-5164