The inducibility and catalytic activity of cytochromes P450c (P450IA1) and P450d (P450IA2) in rat tissues - ScienceDirect

Biochemical Pharmacology

Volume 39, Issue 3, 1 February 1990, Pages 499-506

Biochemical Pharmacology

https://doi.org/10.1016/0006-2952(90)90056-Q Get rights and content

Abstract

The metabolism of phenacetin is primarily by cytochrome P450-dependent O-deethylation to paracetamol (POD activity). In untreated rats, microsomal POD activity is detectable in both the liver and lung, but not in the small intestine or the kidney. POD activity is highly induced in both hepatic and extrahepatic tissues of the rat following treatment with polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (MC). Only cytochrome P450c (P450IA1) is inducible in rat extrahepatic tissues by MC or isosafrole, whereas in the liver both cytochromes P450c and P450d (P450IA2) are inducible by these compounds. Specific antibodies to cytochromes P450c and P450d were used to study the expression and function of these two related isoenzymes in rat liver and extrahepatic tissues before and after induction with MC. Whereas cytochrome P450d is responsible for all of the high affinity POD activity in hepatic microsomal fractions of both untreated and MC treated rats, this activity is mediated only by P450c in microsomal fractions from extrahepatic tissues following MC treatment. POD activity of microsomal fractions from lung of untreated rats was not mediated by either cytochrome P450c or P450d.

References (34)

HN Yeowell et al.
Induction of specific cytochrome P-450 isozymes by methylenedioxyphenyl compounds and antagonism by 3-niethylcholanthrene
Arch Biochem Biophys
(1985)
M Christou et al.
Expression and function of three cytochrome P-450 isozymes in rat extrahepatic tissues
Arch Biochem Biophys
(1987)
DE Ryan et al.
Hepatic microsomal cytochrome P-450 from rats treated with isosafrole. Purification and characterization of four enzymic forms
J Biol Chem
(1980)
LM Reik et al.
Immunochemical relatedness of rat hepatic microsomal cytochromes P-450c and P-450d
J Biol Chem
(1982)
PE Thomas et al.
Induction of two immunochemically related rat liver cytochrome P-450 isozymes, cytochromes P-450c and P-450d, by structurally diverse xenobiotics
J Biol Chem
(1983)
JR Foster et al.
Immunocytochemical localization of cytochrome P-450 in hepatic and extra-hepatic tissues of the rat with a monoclonal antibody against cytochrome P-450c
Biochem Pharmacol
(1986)
PE Thomas et al.
Characterization of nine monoclonal antibodies against rat hepatic cytochrome P450c. Delineation of at least five spatially distinct epitopes
J Biol Chem
(1984)
D Sesardic et al.
High affinity phenacetin O-deethylase is catalysed specifically by cytochrome P450d (P450IA2) in the liver of the rat
Biochem Pharmacol
(1990)
AR Boobis et al.
A monoclonal antibody raised to rat liver cytochrome P-448 (form c) which recognises an epitope common to many other forms of cytochrome P-450
Biochem Pharmacol
(1985)
RJ Edwards et al.
Antibodies to a synthetic peptide that react specifically with a common surface region on two hydrocarbon-inducible isoenzymes of cytochrome P450 in the rat
Biochem Pharmacol
(1988)

R Hawkes et al.

A dot-immunobinding assay for monoclonal and other antibodies

Arch Biochem

(1982)

M Moeremans et al.

Sensitive visualization of antigen-antibody reactions in dot and blot immune overlay assays with immunogold and immunogold/silver staining

J Immmol Methods

(1984)

OH Lowry et al.

Protein measurement with the Folin phenol reagent

J Biol Chem

(1951)

T Omura et al.

The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature

J Biol Chem

(1964)

AR Boobis et al.

Biphasic O-deethylation of phenacetin and 7-ethoxycoumarin by human and rat liver microsomal fractions

Biochem Pharmacol

(1981)

JB Fagan et al.

Noncoordinate regulation of the mRNAs encoding cytochromes P-450_BNF/MC-B and P450_ISF/BNF-G

Arch Biochem Biophys

(1986)

DS Pasco et al.

Transcriptional and post-transcriptional regulation of the genes encoding cytochromes P-450c and P-450d in vivo and in primary hepatocyte cultures

J Biol Chem

(1988)

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^†: Present address: MRC Toxicology Unit, Woodmansterne Road, Carshalton, Surrey SM5 4EF, U.K.

^§: Present address: College of Pharmacy, Rutgers University, Busch Campus, Piscataway, NJ 08855, U.S.A.

Copyright © 1990 Published by Elsevier Inc.