Inhibition and uncoupling of oxidative phosphorylation by nonsteroidal anti-inflammatory drugs: study in mitochondria, submitochondrial particles, cells, and whole heart.
作者： Rafael Moreno-Sánchez , Concepción Bravo , César Vásquez , Guadalupe Ayala , Luis H Silveira
DOI: 10.1016/S0006-2952(98)00330-X
关键词: Cellular respiration 、 Respiratory chain 、 Nimesulide 、 Submitochondrial particle 、 Meloxicam 、 Nabumetone 、 Oxidative phosphorylation 、 Pharmacology 、 Mitochondrion 、 Chemistry 、 Biochemistry
摘要: The effects of the anti-inflammatory drugs diclofenac, piroxicam, indomethacin, naproxen, nabumetone, nimesulide, and meloxicam on mitochondrial respiration, ATP synthesis, membrane potential were determined. Except for nabumetone other stimulated basal uncoupled inhibited collapsed in mitochondria incubated presence either glutamate + malate or succinate. Plots versus synthesis (or respiration) showed proportional variations both parameters, induced by different concentrations meloxicam, but not diclofenac. activity adenine nucleotide translocase was blocked diclofenac nimesulide; also slightly ATPase activity. Naproxen did affect any parameters measured. Nabumetone malate, with NADH oxidation submitochondrial particles nabumetone. O2 uptake intact cells whole heart, whereas five respiration. These observations revealed that situ are an accessible target. a negative inotropic effect cardiac contractility drugs. data indicated indomethacin behaved as uncouplers, exerted specific inhibition site 1 respiratory chain. Diclofenac uncoupler too, it affected H+-ATPase.
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