Kinetic experiments on the binding of metyrapone to liver microsomes

Netter, K.J.; Kahl, Georg F.; Magnussen, M. P.

doi:10.1007/bf01002335

Cited by 58 publications

(4 citation statements)

References 12 publications

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“…Insecticide synergists com petiti vely inhibited naphthalene metabolism in housefly microsomes (49) and ethylmorphine in rat liver microsomes (50). Both metyrapone and re duced metyrapone were fottnd to be competitive inhibitors of the demethyla tion of p-nitroanisole and N-methyl-p-nitroaniline (51).…”

Section: Inhibitjon Of Drug Metabolismmentioning

confidence: 99%

Enhancement and Inhibition of Drug Metabolism

Anders¹

1971

Annu. Rev. Pharmacol.

141

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A large number of factors can alter rates of drug metabolism. This re view wiII discuss the enhancement and inhibition of drug metabolism. By enhancement is meant that increase in rate of in vitro drug metabolism ob served following the inclusion of other drugs or chemicals in the reaction mixture. This term should be distinguished from the enzyme induction re sulting from treatment of the intact animal with other drugs or hydrocar bons. Inhibition of drug metabolism, as used in this review, refers to the blockage of metabolism of one drug by another at the enzymic site. This restriction excludes those agents that reduce rates of drug metabolism by mechanisms other than competition at enzymic sites, such as treatment with carbon tetrachloride (1), morphine (2), thyroxine (3) , and others. In addi tion, the review wiII be restricted to hepatic microsomal mixed function oxi dases; enhancement and inhibition of hydrolytic, reductive, and conjugative pathways will not be considered. ENHANCEMENT OF DRUG METABOLISMEthyl isocyanide.-Imai & Sato (4, 5) reported that EtNC exerts both stimulatory and inhibitory effects on microsomal aniline hydroxylation. The inhibitory effect of EtNC was attributed to a direct competition between oxygen and EtNC. The mechanism of the stimulatory effect appeared to be more complicated. The EtNC concentration producing maximal enhance ment was a function of the aniline concentration; as the aniline concentra tion was increased, more EtNC was needed to produce maximal enhance ment suggesting that hoth compounds were com peting for the same enzyme system. In addition, s pecies differences were observed in the activation of aniline hydroxylation by EtNC. The largest degree of enhancement was ob ta ined in the rabbit; in contrast, EtNC produced only inhibition of aniline

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Section: Inhibitjon Of Drug Metabolismmentioning

confidence: 99%

Enhancement and Inhibition of Drug Metabolism

Anders¹

1971

Annu. Rev. Pharmacol.

141

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“…Metyrapone (2-methyl-1,2-bis(3-pyridyl)-1-propanone) has been shown to inhibit hydroxylation systems present in adrenal cortex mitochondria [1,2], in liver microsomes [3][4][5] or in bacteria [6,7]. Metyrapone interacts with cytochrome P450, as revealed by typical spectral changes [8,9].…”

Section: Introductionmentioning

confidence: 99%

[³H]metyrapol as a tool for studies of interactions of deoxycorticosterone with adrenal cortex mitochondria

Satre¹,

Lunardi²,

Vignais³

1972

FEBS Letters

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“…-propanone), inhibits a number of hydroxylation reactions catalyzed by cytochrome P-450. Metyrapone has a moderately broad spectrum of action for it inhibits steroid hydroxylations at C-ll/3, C-18, and C-19 in adrenal cortex (Dominguez and Samuels, 1963;Sanzari and Perón, 1966;Gaunt et al, 1968;Kahnt and Neher, 1971) and drug hydroxylations in liver microsomes (Leibman, 1969;Netter et al, 1969;Hildebrandt, 1972;Roots and Hildebrandt, 1973a,b) and in bacteria (Peterson et al, 1971;Gunsalus et al, 1971), but it has no effect on the 20aand 22-hydroxylations which are required for cholesterol side-chain cleavage in adrenal cortex mitochondria (Wilson and Harding, 1973) and on the steroid 21-hydroxylation in adrenal cortex microsomes (Dominguez and Samuels, 1963;Sweat et al, 1969a). The inhibitor effect of metyrapone is accompanied by a typical modification of the difference spectrum of P-450, characterized by the appearance of a peak at 427 nm and of a trough at 410 nm and also by a shift in the low-field electron paramagnetic signal of oxidized P-450 (Wilson et al, 1969).…”

mentioning

confidence: 99%

Steroid 11β-hydroxylation in beef adrenal cortex mitochondria. Binding affinity and capacity for specific [¹⁴C]-labeled steroids and for tritium-labeled metyrapol, an inhibitor of the 11β-hydroxylation reaction

Satre¹,

Vignais²

1974

Biochemistry

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Kinetic experiments on the binding of metyrapone to liver microsomes

Cited by 58 publications

References 12 publications

Enhancement and Inhibition of Drug Metabolism

Enhancement and Inhibition of Drug Metabolism

[³H]metyrapol as a tool for studies of interactions of deoxycorticosterone with adrenal cortex mitochondria

Steroid 11β-hydroxylation in beef adrenal cortex mitochondria. Binding affinity and capacity for specific [¹⁴C]-labeled steroids and for tritium-labeled metyrapol, an inhibitor of the 11β-hydroxylation reaction

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Kinetic experiments on the binding of metyrapone to liver microsomes

Cited by 58 publications

References 12 publications

Enhancement and Inhibition of Drug Metabolism

Enhancement and Inhibition of Drug Metabolism

[3H]metyrapol as a tool for studies of interactions of deoxycorticosterone with adrenal cortex mitochondria

Steroid 11β-hydroxylation in beef adrenal cortex mitochondria. Binding affinity and capacity for specific [14C]-labeled steroids and for tritium-labeled metyrapol, an inhibitor of the 11β-hydroxylation reaction

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[³H]metyrapol as a tool for studies of interactions of deoxycorticosterone with adrenal cortex mitochondria

Steroid 11β-hydroxylation in beef adrenal cortex mitochondria. Binding affinity and capacity for specific [¹⁴C]-labeled steroids and for tritium-labeled metyrapol, an inhibitor of the 11β-hydroxylation reaction