EFFECT OF UNCOUPLERS OF OXIDATIVE PHOSPHORYLATION ON OXYGEN UPTAKE, UBIQUINONE REDOX STATUS AND ENERGY-RICH PHOSPHATE LEVELS OF ISOLATED ATRIA
EFFECT OF UNCOUPLERS OF OXIDATIVE PHOSPHORYLATION ON OXYGEN UPTAKE, UBIQUINONE REDOX STATUS AND ENERGY-RICH PHOSPHATE LEVELS OF ISOLATED ATRIA
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DOI：
10.1111/j.1432-1033.1970.tb00828.x
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发表时间：
1970-01-01
期刊：
影响因子：
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通讯作者：
HOFFMANN, PC
中科院分区：
文献类型：
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作者：
LECHNER, V;SIESS, M;HOFFMANN, PC
在与葡萄糖孵育的自发搏动的离体豚鼠心房中，研究了2，4-二硝基苯酚和羰基氰化物-间氯苯腙对收缩幅度和频率、耗氧量和泛醌氧化还原状态的影响。二硝基苯酚（2 - 100 μM）和羰基氰-氯苯腙（0.02-0.4μM）导致收缩幅度降低至对照值的10%，同时氧耗量降低高达20%。泛醌氧化还原状态从32-35%氧化泛醌最大地转变为二硝基苯酚的66%和羰基氰化物-氯苯腙的57%。在与葡萄糖、苹果酸盐或丙酮酸盐孵育的无搏动心房（低Ca++）中进一步检查了二硝基苯酚对氧消耗和泛醌氧化还原状态的影响。与葡萄糖二硝基苯酚导致抑郁症的耗氧量，而与苹果酸或丙酮酸的刺激前药水平的219%和235%，分别观察到。在100 μM二硝基苯酚时，泛醌氧化还原状态向氧化侧移动，并与所有三种底物的呼吸速率相关。在较低浓度的二硝基苯酚下，苹果酸氧化泛醌的程度较低，而丙酮酸或葡萄糖则没有观察到显著的变化。在葡萄糖和苹果酸孵育的无搏动心房中，磷酸肌酸、ATP和丙酮酸的水平随着二硝基苯酚浓度的增加而降低。尽管趋势表明这三种化合物的水平在与葡萄糖孵育的心房中更敏感，但在底物方面未检测到这些效应的显著差异。乳酸水平不受低浓度二硝基酚的影响，在100 μM时升高，与底物无关。结论是氧化磷酸化解偶联剂对完整心房中泛醌氧化还原状态和氧消耗的影响依赖于收缩活性和外源性底物。然而，在用苹果酸盐孵育的非收缩性心房中可以获得用分离的线粒体进行的研究中预期的反应，即在一定范围的二硝基苯酚浓度下刺激氧摄取和泛醌氧化。
The effects of 2,4‐dinitrophenol and carbonyl‐cyanide‐m‐chlorophenylhydrazone on contractile amplitude and frequency, oxygen consumption, and ubiquinone redox status have been examined in spontaneously‐beating isolated guinea pig atria incubated with glucose. Dinitrophenol (2 to 100 μM) and carbonylcyanide‐chlorophenylhydrazone (0.02–0.4μM) lead to depression of contractile amplitude to 10% of control values accompanied by decreases in oxygen consumption of up to 20%. The ubiquinone redox status was shifted maximally from 32–35% oxidized ubiquinone to 66% by dinitrophenol and to 57% by carbonylcyanide‐chlorophenylhydrazone.The effect of dinitrophenol on oxygen consumption and ubiquinone redox status was further examined in non‐beating atria (low Ca++) incubated with glucose, malate or pyruvate. With glucose dinitrophenol led to a depression of oxygen consumption, while with malate or pyruvate a stimulation to 219% and 235% of the predrug level, respectively, was observed. At 100 μM dinitrophenol, ubiquinone redox status was shifted to the oxidized side and correlated with the rate of respiration with all three substrates. At lower concentrations of dinitrophenol, ubiquinone was oxidized to a lesser extent with malate while no significant shift was observed with pyruvate or glucose.Levels of creatine phosphate, ATP and pyruvate were decreased with increasing concentrations of dinitrophenol in non‐beating atria incubated with glucose and malate. No significant difference in these effects was detected with regard to substrate, although the trend indicated that the levels of these three compounds were more sensitive in atria incubated with glucose. Lactate levels were unaffected with low concentrations of dinitrophenol and elevated at 100 μM regardless of substrate.It was concluded that the effect of uncouplers of oxidative phosphorylation on ubiquinone redox status and oxygen consumption in intact atria is dependent upon contractile activity and exogenous substrate. However, the responses expected from studies with isolated mitochondria, namely, stimulation of oxygen uptake and ubiquinone oxidation over a range of dinitrophenol concentrations, can be obtained in non‐contractile atria incubated with malate.