Cytochrome P4502A-mediated coumarin 7-hydroxylation and testosterone hydroxylation in mouse and rat lung

Honkakoski, Paavo, Maenpaa, Jukka, Leikola, Junnu, Pasanen, Markku, Juvonen, Risto, Lang, Matti A., Pelkonen, Olavi and Raunio, Hannu (1993) Cytochrome P4502A-mediated coumarin 7-hydroxylation and testosterone hydroxylation in mouse and rat lung. Pharmacology and Toxicology, 72 2: 107-112.


Author Honkakoski, Paavo
Maenpaa, Jukka
Leikola, Junnu
Pasanen, Markku
Juvonen, Risto
Lang, Matti A.
Pelkonen, Olavi
Raunio, Hannu
Title Cytochrome P4502A-mediated coumarin 7-hydroxylation and testosterone hydroxylation in mouse and rat lung
Journal name Pharmacology and Toxicology   Check publisher's open access policy
ISSN 0901-9928
1742-7843
Publication date 1993-02
Sub-type Article (original research)
Volume 72
Issue 2
Start page 107
End page 112
Total pages 6
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Pulmonary coumarin 7-hydroxylase, testosterone hydroxylase and other P450-mediated activities were compared in the mouse and rat. Coumarin 7-hydroxylase activity was 20 pmol/mg/min. in mouse and 4 pmol/mg/min. in rat lung microsomes. Liver values were 180 (mouse) and 1 (rat) pmol/mg/min. K(m) values of rat and mouse lung coumarin 7-hydroxylase were about 1 μM whereas the rat liver k(m) value was > 100 μM. Phenobarbital and 3-methylcholanthrene did not affect rat lung (or liver) coumarin 7-hydroxylase activity. Anti-Cyp2A-5 antibody effectively inhibited mouse and rat lung coumarin 7-hydroxylase and testosterone 15α-hydroxylations but failed to block these activities in the rat liver. In immunoblot analysis anti-Cyp2a-5 antibody recognized the 50-kDa Cyp2a-4/5 protein in mouse lung microsomes. A P450 protein co-migrating with Cyp2a-5 was also detected in rat lung microsomes. Cyp2a-5 cDNA probe hybridized with a 1.8-kb mRNA species in rat lung RNA fraction. The hybridization signal was not increased by 3-methylcholanthrene or phenobarbital. These data suggest that the mouse lung expresses CYP2A-5 which differs from the liver enzyme only in its regulation and that the rat lung contains a P450 isoform(s) belonging to the 2A subfamily which may be orthologous with the moue Cyp2a-4/5 catalyzing coumarin 7-hydroxylase and testosterone 15α-hydroxylase activities. The recently reported rat lung CYP2A3 (Kimura et al.) gene product is a candidate for the observed coumarin 7-hydroxylase activity in the rat lung.
Keyword Xenobiotic metabolism
Monoclonal antibodies
Liver
Induction
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 29 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 22 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 30 Abstract Views  -  Detailed Statistics
Created: Mon, 30 Nov 2009, 15:02:51 EST