Journal article
Binding of metyrapone to dithionite-reduced cytochrome P-450 from rats treated with xenobiotics
Biochemical pharmacology, Vol.31(21), pp.3489-3494
1982
DOI: 10.1016/0006-2952(82)90631-1
PMID: 7150369
Abstract
The
in vitro binding of metyrapone to dithionite-reduced cytochrome P-450 in hepatic microsomes from rats treated
in vivo with thirteen different xenobiotics was studied spectrophotometrically. The proportion of cytochrome P-450 that bound metyrapone increased 1.8-fold to about 78% following treatment with phenobarbitone (PB) and PB-type inducers (
trans-stilbene oxide, 2,2′,4,4′-tetrachloro-, 2,2′,4,5,5′-pentabromo- and 2,2′,4,4′,5,5′-hexachlorobiphenyl) but remained unaltered following treatment with 3-methylcholanthrene (MC) and MC-type inducers (benzo[
a]pyrene, β-naphthoflavone and 3,3′,4,4′-tetrabromobiphenyl). The simulatenous induction of the PB-inducible and MC-inducible forms of cytochrome P-450 by administering Aroclor 1254 or by coadministering PB with MC increased the proportion of cytochrome P-450 that bound metyrapone to 74 and 78% respectively. PB treatment increased whereas MC treatment decrease the binding affinity for metyrapone by approximately 20-fold. Treatment with isosafrole or metyrapone itself failed to stimulate metyrapone binding. In contrast, pregnenolone-16α-carbonitrile was indistinguishable from PB in its ability to increase the binding capacity and binding affinity for metyrapone. Our results indicate that metyrapone binding is not specific for cytochrome P-450b, the major PB-inducible hemoprotein, as has been proposed [V. Luu-The, J. Cumps and P. Dumont,
Biochem. biophys. Res. Commun.
93, 776 (1980)].
Details
- Title: Subtitle
- Binding of metyrapone to dithionite-reduced cytochrome P-450 from rats treated with xenobiotics
- Creators
- Andrew ParkinsonLarry W RobertsonStephen Safe
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.31(21), pp.3489-3494
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0006-2952(82)90631-1
- PMID
- 7150369
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 1982
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002308302771
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