Inducibility of P450Coh by pyrazole and its derivatives

Kojo, Anneli, Heiskanen, Riitta, Rytköne, Anna-Liisa, Honkakoski, Paavo, Juvonen, Risto and Lang, Matti (1991) Inducibility of P450Coh by pyrazole and its derivatives. Biochemical Pharmacology, 42 9: 1751-1759. doi:10.1016/0006-2952(91)90512-4

Author Kojo, Anneli
Heiskanen, Riitta
Rytköne, Anna-Liisa
Honkakoski, Paavo
Juvonen, Risto
Lang, Matti
Title Inducibility of P450Coh by pyrazole and its derivatives
Formatted title
Inducibility of P450Coh by pyrazole and its derivatives
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 1991-10
Sub-type Article (original research)
DOI 10.1016/0006-2952(91)90512-4
Volume 42
Issue 9
Start page 1751
End page 1759
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract Pyrazole and several of its derivatives increase the hepatic microsomal coumarin 7-hydroxylase to a variable extent. The strongest inducers are pyrazole itself and those derivatives which have a hydroxy group or a halogen at the 4-position of the molecule. The increase in coumarin 7-hydroxylase is due to an increase in the microsomal P450Coh and the corresponding mRNA. The increase of P450Coh by pyrazole and 4-hydroxypyrazole is selective because several other mono-oxygenase enzymes and the total P450 content are either not affected or even decreased. These include the testosterone 15α-hydroxylase (P45015α, a close structural analogue of P450Coh, which is induced only marginally by pyrazole and even decreased by 4-iodopyrazole, and P450ac which is decreased by pyrazole and 4-hydroxypyrazole. Introducing a methyl residue at the 4-position will alter the induction properties of the compound essentially by making it less selective for P450Coh. These results demonstrate the special selective action of pyrazole and some of its derivatives on the hepatic microsomal mono-oxygenase complex and the unique mode of regulation of the cytochrome P450Coh even within the same subfamily of cytochromes P450.
Keyword Coumarin 7 hydroxylase
Mouse liver
High affinity
Cytochrome P-450
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
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Created: Mon, 30 Nov 2009, 15:03:41 EST