Quintanilla A P, Levin M L, Lastre C C, Yokoo H, Levin N W
J Pharmacol Exp Ther. 1979 Dec;211(3):456-9.
The effect of diuretics on incorporation of ADP in mitochondria isolated from rabbit renal cortex and medulla was examined. Inhibition of incorporation of [14 C]ADP into both types of mitochondria was observed following pretreatment with furosemide, ethacrynic acid and meralluride at high drug concentrations (7.5 x 10-4 M furosemide and ethacrynic acid, 6.4 x 10-3 M meralluride). At lower concentrations (7.5 x 10-5 M furosemide and ethacrynic acid, 6.4 x 10-4 M meralluride), only entry of ADP in medullary mitochondria was inhibited. Chlorothiazide, 1.7 x 10-3 M, did not inhibit incorporation of ADP into either mitochondrial preparation. Atractyloside, a classic inhibitor of ADP-ATP exchange, showed inhibition in both preparations. Furosemide, injected in vivo inhibited incorporation of ADP into medullary but not cortical mitochondria. These results are consistent with the possibility that loop diuretics may reduce tubular sodium reabsorption by inhibiting ADP-ATP exchange across the mitochondrial membrane, thereby depriving active transport processes of ATP. The differential action on cortical and medullary mitochondria by loop diuretics is consistent with their predominant site of action in the tubule and with the different morphologic characteristics of both types of mitochondria.
研究了利尿剂对从兔肾皮质和髓质分离的线粒体中ADP掺入的影响。在高药物浓度（7.5×10⁻⁴M速尿和依他尼酸，6.4×10⁻³M汞撒利）下用速尿、依他尼酸和汞撒利预处理后，观察到两种类型线粒体中[¹⁴C]ADP掺入均受到抑制。在较低浓度（7.5×10⁻⁵M速尿和依他尼酸，6.4×10⁻⁴M汞撒利）下，仅髓质线粒体中ADP的进入受到抑制。1.7×10⁻³M的氯噻嗪未抑制ADP掺入任何一种线粒体制剂。阿特拉津，一种经典的ADP-ATP交换抑制剂，在两种制剂中均显示出抑制作用。体内注射速尿抑制ADP掺入髓质线粒体而非皮质线粒体。这些结果与袢利尿剂可能通过抑制跨线粒体膜的ADP-ATP交换来减少肾小管钠重吸收从而剥夺主动转运过程的ATP这一可能性一致。袢利尿剂对皮质和髓质线粒体的不同作用与其在肾小管中的主要作用部位以及两种类型线粒体的不同形态特征一致。
