Simon F R, Gonzalez M, Sutherland E, Accatino L, Davis R A
J Clin Invest. 1980 Apr;65(4):851-60. doi: 10.1172/JCI109737.
The effects of Triton WR-1339 and phenobarbital on ethinyl estradiol bile secretory failure were examined to determine the mechanism responsible for decreased bile salt excretion. When administered to ethinyl estradiol-treated rats, Triton WR-1339 restored bile salt independent bile flow and maximum taurocholate transport, whereas phenobarbital corrected bile flow only. Ethinyl estradiol decreased the activities of Na(+)-K(+)-ATPase, 5'-nucleotidase, while increasing the activities of Mg(++)-ATPase and alkaline phosphatase. In contrast to these heterogeneous changes in surface membrane enzyme activities, the number and affinity of [(14)C]cholic acid carriers were not altered. When administered in vivo or added directly to surface membrane fractions Triton WR-1339 restored the activities of Na(+)-K(+)-ATPase and Mg(++)-ATPase of rats treated with ethinyl estradiol through a process that did not require protein synthesis (unaffected by cycloheximide). Phenobarbital also restored the activity of Na(+)-K(+)-ATPase to control levels, but, unlike Triton WR-1339 it did not correct the defect responsible for reduced bile salt secretion. Ethinyl estradiol increased the concentration of cholesterol esters in surface membrane fractions. When administered to ethinyl estradiol-treated rats, Triton WR-1339 restored cholesterol ester concentrations to normal, whereas phenobarbital did not. These combined data suggest that decreased or altered bile salt carriers or reduced sodium driving forces resulting from impaired activity of Na(+)-K(+)-ATPase are not responsible for decreased bile salt excretion in ethinyl estradiol-treated rats. It is proposed that the diverse changes in surface membrane function, which are associated with ethinyl estradiol bile secretory failure, may be the result of a generalized alteration in membrane lipid structure.
研究了曲拉通WR - 1339和苯巴比妥对乙炔雌二醇胆汁分泌衰竭的影响，以确定胆汁盐排泄减少的机制。给乙炔雌二醇处理的大鼠给药时，曲拉通WR - 1339恢复了不依赖胆汁盐的胆汁流动和最大牛磺胆酸盐转运，而苯巴比妥仅纠正了胆汁流动。乙炔雌二醇降低了Na(+)-K(+)-ATP酶、5'-核苷酸酶的活性，同时增加了Mg(++)-ATP酶和碱性磷酸酶的活性。与这些表面膜酶活性的异质性变化相反，[(14)C]胆酸载体的数量和亲和力没有改变。当在体内给药或直接添加到表面膜组分中时，曲拉通WR - 1339通过一个不需要蛋白质合成的过程（不受环己酰亚胺影响）恢复了乙炔雌二醇处理大鼠的Na(+)-K(+)-ATP酶和Mg(++)-ATP酶的活性。苯巴比妥也将Na(+)-K(+)-ATP酶的活性恢复到对照水平，但与曲拉通WR - 1339不同的是，它没有纠正导致胆汁盐分泌减少的缺陷。乙炔雌二醇增加了表面膜组分中胆固醇酯的浓度。给乙炔雌二醇处理的大鼠给药时，曲拉通WR - 1339将胆固醇酯浓度恢复到正常水平，而苯巴比妥则没有。这些综合数据表明，乙炔雌二醇处理的大鼠中胆汁盐排泄减少不是由于胆汁盐载体减少或改变，也不是由于Na(+)-K(+)-ATP酶活性受损导致的钠驱动力降低。有人提出，与乙炔雌二醇胆汁分泌衰竭相关的表面膜功能的多种变化可能是膜脂质结构普遍改变的结果。
