Abstract
Although PK11195 binds to the peripheral benzodiazepine receptor with nanomolar affinity, significant data exist which suggest that it has another cellular target distinct from the PBR. Here we demonstrate that PK11195 inhibits F(1)F(0)-ATPase activity in an OSCP-dependent manner, similar to the pro-apoptotic benzodiazepine Bz-423. Importantly, our data indicate that cellular responses observed with micromolar concentrations of PK11195, which are commonly attributed to modulation of the PBR, are likely a direct result of mitochondrial F(1)F(0)-ATPase inhibition.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine Triphosphate / metabolism
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Antineoplastic Agents / metabolism
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Apoptosis / drug effects
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Benzodiazepines / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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GABA-A Receptor Antagonists*
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Humans
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Hydrolysis
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Isoquinolines / metabolism
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Kinetics
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Ligands
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Mitochondria / enzymology*
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Proton-Translocating ATPases / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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GABA-A Receptor Antagonists
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Isoquinolines
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Ligands
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Benzodiazepines
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Adenosine Triphosphate
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Proton-Translocating ATPases
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PK 11195