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  • Title: Pentamidine is an uncoupler of oxidative phosphorylation in rat liver mitochondria.
    Author: Moreno SN.
    Journal: Arch Biochem Biophys; 1996 Feb 01; 326(1):15-20. PubMed ID: 8579363.
    Abstract:
    Pentamidine is a cationic drug that is used for the treatment of African trypanosomiasis, leishmaniasis, and Pneumocystis carinii pneumonia. When incubated with pharmacological concentrations of pentamidine, some of the etiologic agents of those diseases reach internal concentrations close to 1.0 mM. In this work pentamidine is shown to exhibit characteristics of a cationic uncoupler of oxidative phosphorylation in isolated rat liver mitochondria: it released respiratory control, enhanced the latent ATPase activity, and released the inhibition of State 3 respiration by oligomycin. Maximal stimulation of respiration and ATPase activity was observed at a concentration of pentamidine of 200-300 microM. Higher concentrations had an inhibitory effect on mitochondrial respiration. As it happens with other cationic uncouplers, the uncoupling effect of pentamidine required inorganic phosphate. Pentamidine-induced uncoupling of oxidative phosphorylation was accompanied by an efflux of Ca2+ from the mitochondria and partial collapse of the mitochondrial membrane potential.
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