Abstract
MI-D (4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylami ne chloride), a new mesoionic compound, depressed the phosphorylation efficiency of liver mitochondria as deduced from an accentuated decrease of the respiratory control coefficient and ADP/O ratio. Analysis of segments of the respiratory chain suggested that the MI-D inhibition site is further on than complex I and between complexes II and III. The transmembrane electrical potential (delta psi) was collapsed dependent on MI-D concentration. ATPase activity was dramatically increased by MI-D in intact mitochondria, but inhibited in carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled mitochondria. These results suggest that MI-D acts as an uncoupler agent, a property closely related to its structural characteristics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Diphosphate / metabolism
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Adenosine Triphosphatases / metabolism
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Animals
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Cell Respiration / drug effects*
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Cinnamates / pharmacology*
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Dose-Response Relationship, Drug
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Electron Transport / drug effects
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Glutamic Acid / metabolism
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Male
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Membrane Potentials / drug effects
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Mitochondria, Liver / enzymology
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Mitochondria, Liver / metabolism*
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Oxidative Phosphorylation / drug effects
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Oxidoreductases / metabolism
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Oxygen / metabolism
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Rats
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Rats, Wistar
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Succinic Acid / metabolism
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Thiadiazoles
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Thiazoles / pharmacology*
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Uncoupling Agents / pharmacology*
Substances
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4-phenyl-5-(4-nitrocinnamoyl)-1,3,4-thiadiazolium-2-phenylamine
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Cinnamates
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Thiadiazoles
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Thiazoles
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Uncoupling Agents
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Glutamic Acid
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Adenosine Diphosphate
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Succinic Acid
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Oxidoreductases
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Adenosine Triphosphatases
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Oxygen