Alpert S, Mosher M, Shanske A, Arias I M
J Gen Physiol. 1969 Feb;53(2):238-47. doi: 10.1085/jgp.53.2.238.
Previous studies based upon competition between different organic anions for biliary excretion in vivo have suggested that all organic anions share a common hepatic secretory mechanism. Corriedale sheep with an inherited defect in organic anion excretion by the liver were used to study this problem directly without the need for competition studies, the results of which are difficult to analyze. Maximal biliary excretion of sulfobromphthalein (BSP) in mutant Corriedale sheep was less than 7% of that observed in normal sheep whereas maximal biliary excretion of taurocholate, the major organic anion in sheep bile, was not different in mutant and normal sheep. Taurocholate infusion enhanced maximal hepatic excretion of BSP in normal but not in mutant sheep. These studies of an inheritable disorder which appears to be identical to the Dubin-Johnson syndrome in man, demonstrate that taurocholate excretion requires at least one step in biliary excretion which is not required by other organic anions such as bile pigment, porphyrins, drugs, and dyes.
以往基于不同有机阴离子在体内胆汁排泄过程中的竞争关系开展的研究表明,所有有机阴离子都共享一种常见的肝脏分泌机制。利用患有肝脏有机阴离子排泄遗传缺陷的考力代绵羊直接研究这一问题,无需进行竞争研究,因为竞争研究的结果难以分析。突变型考力代绵羊中磺溴酞钠(BSP)的最大胆汁排泄量不到正常绵羊的7%,而绵羊胆汁中的主要有机阴离子牛磺胆酸盐的最大胆汁排泄量在突变型和正常绵羊中并无差异。输注牛磺胆酸盐可增强正常绵羊而非突变型绵羊中BSP的最大肝脏排泄量。这些针对一种似乎与人的杜宾-约翰逊综合征相同的遗传性疾病的研究表明,牛磺胆酸盐的排泄在胆汁排泄中至少需要一个其他有机阴离子(如胆色素、卟啉、药物和染料)不需要的步骤。