Shimamura H, Suzuki H, Tagaya O, Horie T, Sugiyama Y
Traditional Chinese Medicine Research Laboratory, Kanebo Ltd., Osaka, Japan.
Pharm Res. 1996 Dec;13(12):1833-7. doi: 10.1023/a:1016033124819.
To examine the presence of multiplicity for the biliary excretion of xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) glucuronides.
GR was administered intravenously as a bolus to Sprague-Dawley (SD) rats which received an i.v. infusion of inhibitors (dibromosulfophthalein (DBSP) and indocyanine green (ICG)) at their transport maximum rates. Biliary excretion of GR was also examined in Eisai hyperbilirubinemic rats (EHBR), which have a hereditary defect in the canalicular transport system of several organic anions.
Infusion of ICG did not affect the biliary excretion of GR, whereas infusion of DBSP reduced it significantly. The plasma concentration of GR was increased by DBSP but not by ICG. In EHBR, the biliary excretion of GR was severely impaired, resulting in an increase in the plasma concentration of GR.
These findings suggest (1) that the biliary excretion of GR is mediated by the system which is shared by DBSP and LG glucuronides but not by ICG and (2) that this system is hereditarily defective in EHBR. Together with our previous findings, the multiplicity for the biliary excretion of organic anions is shown.
为了研究外源性生物结合物经胆汁排泄的多重性，我们研究了甘草酸（GR）的处置情况，甘草酸在其分子结构中含有葡萄糖醛酸，并且具有抑制甘草次酸（LG）葡萄糖醛酸苷经胆汁排泄的能力。
将GR以静脉推注的方式给予Sprague-Dawley（SD）大鼠，这些大鼠以其最大转运速率静脉输注抑制剂（二溴磺酞钠（DBSP）和吲哚菁绿（ICG））。还在艾司ai高胆红素血症大鼠（EHBR）中检测了GR的胆汁排泄情况，这些大鼠在几种有机阴离子的胆小管转运系统中存在遗传性缺陷。
输注ICG不影响GR的胆汁排泄，而输注DBSP则使其显著降低。DBSP可使GR的血浆浓度升高，但ICG不会。在EHBR中，GR的胆汁排泄严重受损，导致GR的血浆浓度升高。
这些发现表明：（1）GR的胆汁排泄是由DBSP和LG葡萄糖醛酸苷共同的系统介导的，而不是由ICG介导的；（2）该系统在EHBR中存在遗传性缺陷。结合我们之前的发现，显示了有机阴离子胆汁排泄的多重性。
