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Action of metyrapone on the redox state of free nicotinamide-adenine dinucleotide and on oxygen consumption of perfused rat livers and isolated mitochondria

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Summary

Metyrapone [2-methyl-1,2-bis-(3-pyridyl)-1-propanone] in a concentration of 5 mM increased the lactate/pyruvate ratio and theΒ-hydroxybutyrate/ acetoacetate ratio in the perfusion fluid of the isolated rat liver by a factor of 6 indicating a considerable shift in the ratio of free [NAD]/[NADH] in both the cytoplasmic and the mitochondrial compartment. Oxygen uptake of the isolated liver was decreased to about one half. The onset of the inhibitory effect on the respiration of the isolated organ was immediate. The inhibition lasted for at least 1 h.

In experiments with isolated mitochondria utilizingΒ-hydroxybutyrate as a substrate, a decrease of the respiration rate and of the rate of ferricyanide reduction to about one half was observed after the addition of 5 mM metyrapone. Thein vitro findings indicate that the effect of metyrapone on the metabolic state of the isolated organ is due to an attack by the substance on the respiratory chain. The entrance of hydrogen into the chain mediated byΒ-hydroxybutyrate dehydrogenase as well as the terminal oxidation in the chain were not affected by metyrapone.

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Authors and Affiliations

  1. Pharmakologisches Institut, Abteilung für Toxikologie, der UniversitÄt Mainz, Deutschland

    G. F. Kahl & S. Simon

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  1. G. F. Kahl
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  2. S. Simon
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Additional information

The experiments were carried out with the financial support of the Deutsche Forschungsgemeinschaft. Some of the equipment was provided by the Stiftung Volkswagenwerk.

We thank Professor Dr. W. Staib, Düsseldorf, for the demonstration of his liver perfusion technique.

The able and careful technical assistance of Miss Ingeborg Raab is gratefully acknowledged.

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Kahl, G.F., Simon, S. Action of metyrapone on the redox state of free nicotinamide-adenine dinucleotide and on oxygen consumption of perfused rat livers and isolated mitochondria. Naunyn-Schmiedebergs Arch. Pharmak. 268, 1–16 (1971). https://doi.org/10.1007/BF00997168

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  • DOI: https://doi.org/10.1007/BF00997168

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