Kuipers F, Radominska A, Zimniak P, Little J M, Havinga R, Vonk R J, Lester R
Department of Pediatrics, University of Gronigen, The Netherlands.
J Lipid Res. 1989 Dec;30(12):1835-45.
Biliary secretion of bile acid glucuronides was studied in control rats and in rats with a congenital defect in hepatobiliary transport of organic anions (GY rats). In control animals, hepatobiliary transport of [3H]lithocholic acid 3-O-glucuronide and [3H]cholic acid 3-O-glucuronide was efficient (greater than 95% in 1 h) and comparable to that of [14C]taurocholic acid. Secretion of both glucuronides was impaired in GY rats (24% and 71% at 1 h), whereas that of taurocholate was similar to control values. However, recovery of the glucuronides in bile was nearly complete within 24 h; virtually no radioactivity was found in urine. In control rats, biliary secretion of lithocholic acid 3-O-glucuronide, but not that of cholic acid 3-O-glucuronide or taurocholate, could be delayed by simultaneous infusion of dibromosulphthalein. In mutant rats, dibromosulphthalein infusion was also able to inhibit secretion of cholic acid 3-O-glucuronide. [3H]Hydroxyetianic acid, a C20 short-chain bile acid, was secreted by control rats as a mixture of 20% carboxyl-linked and 80% hydroxyl-linked (3-O-)glucuronide; secretion was very efficient (99% in 1 h). In GY rats, secretion was drastically impaired (16% at 1 h and 74% over a 24-h period). Initially, the mutant secreted more carboxyl- than hydroxyl-linked glucuronide, but the ratio reached that of control animals after 24 h. The rates of formation of both types of hydroxyetianic acid glucuronide by hepatic microsomes from mutant rats were similar or even slightly higher than those of control microsomes. These findings indicate that bile acid 3-O-glucuronides, but probably not carboxyl-linked glucuronides, are secreted into bile by a transport system shared with organic anions such as conjugated bilirubin and dibromosulphthalein, but different from that for amino acid-conjugated bile acids.
在对照大鼠和患有先天性有机阴离子肝胆转运缺陷的大鼠（GY大鼠）中研究了胆汁酸葡糖醛酸苷的胆汁分泌情况。在对照动物中，[3H]石胆酸3-O-葡糖醛酸苷和[3H]胆酸3-O-葡糖醛酸苷的肝胆转运效率很高（1小时内大于95%），与[14C]牛磺胆酸的转运效率相当。两种葡糖醛酸苷的分泌在GY大鼠中均受损（1小时时分别为24%和71%），而牛磺胆酸盐的分泌与对照值相似。然而，葡糖醛酸苷在胆汁中的回收率在24小时内几乎完全；尿液中几乎未发现放射性。在对照大鼠中，同时输注二溴磺酞钠可延迟石胆酸3-O-葡糖醛酸苷的胆汁分泌，但胆酸3-O-葡糖醛酸苷或牛磺胆酸盐的分泌不受影响。在突变大鼠中，输注二溴磺酞钠也能够抑制胆酸3-O-葡糖醛酸苷的分泌。[3H]羟雌酮酸，一种C20短链胆汁酸，在对照大鼠中以20%羧基连接和80%羟基连接（3-O-）葡糖醛酸苷的混合物形式分泌；分泌效率非常高（1小时内为99%）。在GY大鼠中，分泌严重受损（1小时时为16%，24小时期间为74%）。最初，突变体分泌的羧基连接葡糖醛酸苷比羟基连接葡糖醛酸苷多，但24小时后该比例达到对照动物的水平。来自突变大鼠的肝微粒体形成两种类型羟雌酮酸葡糖醛酸苷的速率与对照微粒体相似，甚至略高。这些发现表明，胆汁酸3-O-葡糖醛酸苷，而非羧基连接的葡糖醛酸苷，是通过与有机阴离子（如结合胆红素和二溴磺酞钠）共用的转运系统分泌到胆汁中的，但不同于氨基酸结合胆汁酸的转运系统。
