Cytochrome P-4503A1 catalyzes the formation of MA1 from territrem a in liver microsomes of 7-week-old female Wistar rats.

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Lin Wu SW, Jean WC, Peng FC, Edwards RJ

Cytochrome P-4503A1 catalyzes the formation of MA1 from territrem a in liver microsomes of 7-week-old female Wistar rats.

J Toxicol Environ Health A. 2003 Mar 14;66(5):453-67.

PubMed ID

12712632 [ View in PubMed

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Abstract

Liver microsomal territrem A (TRA) metabolism was studied in 7-wk-old female Wistar rats. Pretreatment with phenobarbital (PB) or dexamethasone (DEX) resulted in a significant increase in 4 beta-hydroxymethyl-4 beta-demethylterritrem A (MA1) production. SKF 525A (0.025 and 0.05 mM), a general cytochrome P-450 (CYP450) inhibitor, blocked MA1 formation in liver microsomes from PB-pretreated female rats. Anti-CYP2B antibody had no marked effect on MA1 formation, although orphenadrine (0.5 mM), which inhibits CYP2B, blocked MA1 formation in liver microsomes from PB-treated female rats. An immunoinhibition study showed that anti-CYP3A2 antibody reduced MA1 formation to nondetectable levels in liver microsomes from PB-treated female rats. Furthermore, immunoblotting showed that CYP3A1 protein was expressed in 7-wk-old female rat and only MA1 was formed from TRA using supersomes from CYP3A1-expressing baculovirus-infected insect cells. Further, Western blot analysis indicated that CYP3A2 protein was expressed in 2-wk-old rats of both sexes and 7-wk-old male rats, and 3 metabolites of TRA, such as MA1, MAX, and MA2, were formed using supersomes from CYP3A2-expressing baculovirus-infected insect cells. These results suggest that MA1 formation in liver microsomes of 7-wk-old female Wistar rats is mediated by CYP3A1.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Orphenadrine	Cytochrome P450 2B6	Protein	Humans	Unknown	Inhibitor	Details