van Rossum G D, Ernst S A
J Membr Biol. 1978 Oct 19;43(2-3):251-75. doi: 10.1007/BF01933482.
Ethacrynic acid greatly inhibited net transport of ions and aerobic, energy-conserving metabolism in slices of avian salt gland, rat liver, and rat and guinea-pig kidney cortex. The effects of increasing concentrations of ethacrynic acid on the transport of Na+, K+ and Cl- ran closely parallel to its effects on tissue ATP levels and respiration. The concentration needed for maximal inhibition of transport reduced ATP levels by 80--90%. Respiration was reduced by 80--90% in salt gland and kidney cortex, and by a maximum of 30% in liver slices. The effects of low concentrations of ethacrynic acid required time to become fully manifest in some tissues, and the development of transport inhibition followed a similar course to decline of respiration and ATP levels. Ca2+ extrusion by liver cells was inhibited by ethacrynic acid. The concentration dependence of the inhibition was similar to that shown by the other transport systems inhibited. There was no distinction evident between the sensitivity of Na+ extrusion and of K+ accumulation to the diuretic. Lactate production increased as respiration decreased in the presence of increasing concentrations of ethacrynic acid. We conclude that ethacrynic acid acted primarily as an inhibitor of mitochondrial respiration and ATP synthesis in the tissue slices, and that inhibition of ion transport was a nonspecific consequence of the failure of the energy supply.
依他尼酸能显著抑制禽盐腺、大鼠肝脏以及大鼠和豚鼠肾皮质切片中的离子净转运以及有氧的、保存能量的代谢过程。依他尼酸浓度升高对Na⁺、K⁺和Cl⁻转运的影响与其对组织ATP水平和呼吸作用的影响密切平行。最大程度抑制转运所需的浓度可使ATP水平降低80% - 90%。盐腺和肾皮质中的呼吸作用降低80% - 90%，肝脏切片中最多降低30%。低浓度依他尼酸的作用在某些组织中需要时间才能完全显现，转运抑制的发展过程与呼吸作用和ATP水平的下降过程相似。肝细胞的Ca²⁺外排受到依他尼酸的抑制。抑制作用的浓度依赖性与其他受抑制的转运系统相似。Na⁺外排和K⁺蓄积对利尿剂的敏感性之间没有明显差异。在依他尼酸浓度增加的情况下，随着呼吸作用的降低，乳酸生成增加。我们得出结论，依他尼酸在组织切片中主要作为线粒体呼吸作用和ATP合成的抑制剂起作用，并且离子转运的抑制是能量供应不足的非特异性结果。
