Ebner K V, Braselton W E
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Chem Biol Interact. 1987;63(2):139-55. doi: 10.1016/0009-2797(87)90094-9.
Rat hepatic mitochondrial permeability and succinate + valinomycin-dependent swelling were studied in the presence of hydroxy derivatives of polychlorinated biphenyls (PCBOHs), Aroclor 1254 (ARO) and combinations of both. PCBOHs with two or more chlorines and pKas greater than 8.0 (PCBOH I) induced passive swelling in a potassium acetate-sucrose medium (pH 7.2), maximally stimulated succinate respiration, and suppressed ADP-stimulated H+ uptake. Mono- and certain dichlorinated biphenylols with similar high pKas (PCBOH II) were ineffective. Para-hydroxy PCBs with chlorines substituted in the 3,5 positions and with pKas near 6.8 (PCBOH III) inhibited succinate + valinomycin swelling and ADP-stimulated H+ and oxygen uptake. The efficacy of both PCBOH I and III derivatives required the presence of a hydroxyl moiety and increased directly with the degree of chlorination. Coplanarity was not a determining factor for PCBOH I compounds. ARO activated succinate + valinomycin swelling at low concentrations (3-25 nmol/mg protein) but inhibited at higher concentrations (greater than 40 nmol/mg). Activating concentrations of ARO potentiated the influence of PCBOHs on mitochondria. The uncoupling effects of the PCBOHs and ARO involved permeability changes of the inner membrane, respiratory inhibition, or combinations of both.
在多氯联苯羟基衍生物（PCBOHs）、Aroclor 1254（ARO）以及二者组合存在的情况下，研究了大鼠肝脏线粒体通透性以及琥珀酸+缬氨霉素依赖性肿胀。具有两个或更多氯原子且pKa大于8.0的PCBOHs（PCBOH I）在醋酸钾-蔗糖培养基（pH 7.2）中诱导被动肿胀，最大程度刺激琥珀酸呼吸，并抑制ADP刺激的H⁺摄取。具有相似高pKa的单氯和某些二氯联苯醇（PCBOH II）无效。在3,5位被氯取代且pKa接近6.8的对羟基多氯联苯（PCBOH III）抑制琥珀酸+缬氨霉素肿胀以及ADP刺激的H⁺摄取和氧气摄取。PCBOH I和III衍生物的效力都需要羟基部分的存在，并且直接随氯化程度增加。共面性不是PCBOH I化合物的决定性因素。低浓度（3 - 25 nmol/mg蛋白质）时ARO激活琥珀酸+缬氨霉素肿胀，但高浓度（大于40 nmol/mg）时抑制。ARO的激活浓度增强了PCBOHs对线粒体的影响。PCBOHs和ARO的解偶联作用涉及内膜通透性变化、呼吸抑制或二者的组合。
