Schölmerich J, Schmidt K, Kremer B, Becher M S, Gerok W
Klin Wochenschr. 1981 Jun 15;59(12):655-68. doi: 10.1007/BF02593857.
Alterations of cellular membranes under the influence of bile acids seem to be of pathophysiological importance in cholestasis. The effect of taurolithocholic acid (TLCA) and chenodeoxycholic acid (CDCA) on membrane structure and release of cellular enzymes was studied on isolated rat hepatocytes. The response of urea synthesis to glucagon was used as a parameter of membrane function. The threshold dose of TLCA, marked by rapidly increasing enzyme release, was about 100 micrometers, whereas that of CDCA was between 500 and 1,000 micrometers. Addition of albumin (1 g-%) increased the threshold dose of CDCA; this occurred for TLCA only 8 g-%. Electron-microscopical alterations of the endoplasmic reticulum and submembranous areas were found with concentrations below these threshold doses even in the presence of albumin. These alterations are interpreted as disturbance of cellular transport and energy metabolism. TLCA inhibited glucagon response of cells in concentrations below 100 micrometers. These results demonstrate an influence of the bile acids studied on structure and function of liver cell membranes, which may be of importance in the pathogenesis of cholestasis. The rough endoplasmic reticulum could be another cellular structure which is affected by these bile acids.
在胆汁酸的影响下,细胞膜的改变在胆汁淤积中似乎具有病理生理学意义。在分离的大鼠肝细胞上研究了牛磺石胆酸(TLCA)和鹅去氧胆酸(CDCA)对膜结构和细胞酶释放的影响。尿素合成对胰高血糖素的反应被用作膜功能的一个参数。以酶释放迅速增加为标志的TLCA阈值剂量约为100微摩尔,而CDCA的阈值剂量在500至1000微摩尔之间。添加白蛋白(1 g-%)可增加CDCA的阈值剂量;而对于TLCA,仅在白蛋白浓度为8 g-%时才会出现这种情况。即使存在白蛋白,在低于这些阈值剂量的浓度下也发现内质网和膜下区域有电子显微镜下的改变。这些改变被解释为细胞转运和能量代谢的紊乱。TLCA在浓度低于100微摩尔时抑制细胞对胰高血糖素的反应。这些结果表明所研究的胆汁酸对肝细胞膜的结构和功能有影响,这在胆汁淤积的发病机制中可能具有重要意义。粗面内质网可能是受这些胆汁酸影响的另一种细胞结构。