Hardison W G, Dalle-Molle E, Gosink E, Lowe P J, Steinbach J H, Yamaguchi Y
Department of Medicine, Veterans Administration Medical Center, San Diego 92161.
Am J Physiol. 1991 Jan;260(1 Pt 1):G167-74. doi: 10.1152/ajpgi.1991.260.1.G167.
To determine the effects of alteration of biliary paracellular permeability on bile flow and composition, we measured the biliary outputs of compounds highly concentrated in bile, all infused at a constant rate in the isolated rat liver perfused with Krebs-Henseleit buffer in a one-pass fashion. Paracellular permeability was increased by infusing 10(-8) M vasopressin (VP). The cholephilic compounds were three cations of various molecular weights, tributylmethylammonium (TBuMA), N-acetylprocainamide ethobromide (APAEB), and propidium iodide, and two anions, taurocholate (TC), a micelle-forming bile acid, and taurodehydrocholate (TDHC), an nonmicelle former. When TC was infused and paracellular permeability increased with VP, neither bile flow nor TC output changed, whereas outputs of cations fell. When TDHC was infused, TDHC output fell, as did outputs of all cations. The decrements in cation outputs exceeded that of TDHC and were inversely related to the molecular weight of the cation. To document that these changes were not related to reduced uptake of these compounds, we tested the uptakes of TBuMA, APAEB, and TDHC into isolated hepatocytes. In no case did 10(-8) M VP significantly reduce uptake. The data demonstrate that micelle-forming bile acids, with their high effective molecular weights, do not efflux from the biliary tree when permeability is increased with VP, whereas nonmicelle-forming bile acids do. Cations efflux more readily than anions, and within this group efflux rate is inversely related to molecular weight. The data confirm the size and charge selectivity of biliary tree permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
为了确定胆管旁细胞通透性改变对胆汁流量和成分的影响，我们测量了胆汁中高度浓缩的化合物的胆汁输出量，所有化合物均以恒定速率一次性注入用 Krebs-Henseleit 缓冲液灌注的离体大鼠肝脏中。通过注入 10(-8) M 血管加压素（VP）增加旁细胞通透性。亲胆化合物有三种不同分子量的阳离子，三丁基甲基铵（TBuMA）、N-乙酰普鲁卡因酰胺乙溴化物（APAEB）和碘化丙啶，以及两种阴离子，形成微胶粒的胆汁酸牛磺胆酸盐（TC）和非微胶粒形成剂牛磺脱氢胆酸盐（TDHC）。当注入 TC 且用 VP 增加旁细胞通透性时，胆汁流量和 TC 输出量均未改变，而阳离子输出量下降。当注入 TDHC 时，TDHC 输出量下降，所有阳离子的输出量也下降。阳离子输出量的减少超过了 TDHC 的减少，且与阳离子的分子量呈负相关。为了证明这些变化与这些化合物摄取减少无关，我们测试了 TBuMA、APAEB 和 TDHC 对离体肝细胞的摄取。在任何情况下，10(-8) M VP 均未显著降低摄取。数据表明，当用 VP 增加通透性时，具有高有效分子量的形成微胶粒的胆汁酸不会从胆管树中流出，而非形成微胶粒的胆汁酸则会流出。阳离子比阴离子更容易流出，并且在这一组中，流出速率与分子量呈负相关。数据证实了胆管树通透性的大小和电荷选择性。（摘要截断于 250 字）
