Binding of metyrapone to dithionite-reduced cytochrome P-450 from rats treated with xenobiotics
Identifieur interne : 005139 ( Main/Exploration ); précédent : 005138; suivant : 005140Binding of metyrapone to dithionite-reduced cytochrome P-450 from rats treated with xenobiotics
Auteurs : Andrew Parkinson [Canada] ; Larry W. Robertson [Canada] ; Stephen Safe [Canada]Source :
- Biochemical Pharmacology [ 0006-2952 ] ; 1982.
English descriptors
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)].
Url:
DOI: 10.1016/0006-2952(82)90631-1
Affiliations:
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Robertson</name></author><author><name sortKey="Safe, Stephen" sort="Safe, Stephen" uniqKey="Safe S" first="Stephen" last="Safe">Stephen Safe</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D90A92DD357817D7EDDB3DEF17A44802327ED290</idno><date when="1982" year="1982">1982</date><idno type="doi">10.1016/0006-2952(82)90631-1</idno><idno type="url">https://api-v5.istex.fr/document/D90A92DD357817D7EDDB3DEF17A44802327ED290/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000760</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000760</idno><idno type="wicri:Area/Istex/Curation">000760</idno><idno type="wicri:Area/Istex/Checkpoint">002700</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">002700</idno><idno type="wicri:doubleKey">0006-2952:1982:Parkinson A:binding:of:metyrapone</idno><idno type="wicri:Area/Main/Merge">005B52</idno><idno type="wicri:Area/Main/Curation">005139</idno><idno type="wicri:Area/Main/Exploration">005139</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Binding of metyrapone to dithionite-reduced cytochrome P-450 from rats treated with xenobiotics</title><author><name sortKey="Parkinson, Andrew" sort="Parkinson, Andrew" uniqKey="Parkinson A" first="Andrew" last="Parkinson">Andrew Parkinson</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>The Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea><wicri:noRegion>Ontario N1G 2W1</wicri:noRegion></affiliation></author><author><name sortKey="Robertson, Larry W" sort="Robertson, Larry W" uniqKey="Robertson L" first="Larry W." last="Robertson">Larry W. Robertson</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>The Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea><wicri:noRegion>Ontario N1G 2W1</wicri:noRegion></affiliation></author><author><name sortKey="Safe, Stephen" sort="Safe, Stephen" uniqKey="Safe S" first="Stephen" last="Safe">Stephen Safe</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>The Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry, University of Guelph, Guelph, Ontario N1G 2W1</wicri:regionArea><wicri:noRegion>Ontario N1G 2W1</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Biochemical Pharmacology</title><title level="j" type="abbrev">BCP</title><idno type="ISSN">0006-2952</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1982">1982</date><biblScope unit="volume">31</biblScope><biblScope unit="issue">21</biblScope><biblScope unit="page" from="3489">3489</biblScope><biblScope unit="page" to="3494">3494</biblScope></imprint><idno type="ISSN">0006-2952</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-2952</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>BNF</term><term>B[a]P benzo[a]pyrene</term><term>CO</term><term>HCBP</term><term>MC</term><term>PB</term><term>PBBP</term><term>PCN</term><term>TBBP</term><term>TCBP</term><term>TSO</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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)].</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Parkinson, Andrew" sort="Parkinson, Andrew" uniqKey="Parkinson A" first="Andrew" last="Parkinson">Andrew Parkinson</name></noRegion><name sortKey="Robertson, Larry W" sort="Robertson, Larry W" uniqKey="Robertson L" first="Larry W." last="Robertson">Larry W. Robertson</name><name sortKey="Safe, Stephen" sort="Safe, Stephen" uniqKey="Safe S" first="Stephen" last="Safe">Stephen Safe</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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