A study on the vesicular transport of canalicular transporters

秋水仙碱是一种胞内囊泡转运的抑制剂，曾被报道可抑制胆汁酸和有机阴离子的排泄，但以前的研究结果是有争议的，为了系统地评价秋水仙碱对胆汁中亲胆化合物排泄的影响，我们研究了秋水仙碱对各种小管转运蛋白底物的胆汁排泄的影响。将各种小管转运蛋白的底物以其最大排泄速率或高于其最大排泄速率输注到大鼠体内，并研究了秋水仙碱对其胆汁排泄的影响。秋水仙碱对牛磺胆酸盐的胆汁排泄有明显的抑制作用，而对牛磺熊去氧胆酸盐的胆汁排泄无明显的抑制作用。P-底物，结果表明，秋水仙素对牛磺胆酸和牛磺熊去氧胆酸的最大排泄量不同，秋水仙素对这两种胆汁酸的排泄影响也不同是这些胆汁酸缀合物将Bsep囊泡靶向至小管膜的不同调节机制。Mrp 2和P-gp的囊泡靶向小管膜被认为是秋水仙碱不敏感的情况下，胆汁酸共同管理。

Colchicine, an inhibitor of the intracellular vesicular transport, has been reported to inhibit the biliary excretion of bile acids and organic anions, but the previous findings are controversial.In order to systematically evaluate the effect of colchicine on the biliary excretion of cholephilic compounds, we studied the effect of colchicines on the biliary excretion of substrates of various canalicular transporters. Substrates of various canalicular transporters were infused at the rate of or above their excretory maximum into rats, and the effect of colchicine on their biliary excretion was studied. The biliary excretion of taurocholate was markedly inhibited by colchicine, whereas that of tauroursodeoxycholate was not inhibited.The biliary excretory maximum of taurolithocholate-sulfate and sulfobromophthalein, substrates of mrp2, that of erythromycin, a substrate of P-gp were not affected by colchicine.The different excretory maximum of taurocholate and tauroursodeoxycholate and the different effect of colchicine on the excretion of these bile acids are considered to be different regulatory mechanisms of vesicular targeting of the Bsep to the canalicular membrane by these bile acid conjugates. The vesicular targeting of Mrp2 and the P-gp to the canalicular membrane is considered to be colchicine insensitive in the absence of bile acid coadministration.