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Transcellular transport of organic anions in the isolated perfused rat liver: The differential effects of monensin and colchicine
Author(s) -
Aoyama Nankei,
Ohya Toshihide,
Chandler Kimberly,
Gresky Susan,
Holzbach R. Thomas
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840140102
Subject(s) - monensin , transcellular , colchicine , chemistry , ouabain , paracellular transport , golgi apparatus , organic anion , biochemistry , biophysics , flux (metallurgy) , sodium , taurine , salt (chemistry) , medicine , biology , endoplasmic reticulum , membrane , amino acid , organic chemistry , ion , permeability (electromagnetism)
Nonbile salt cholephiles and bile salts are two classes of organic anions that are efficiently taken up and excreted by the liver. Recent evidence suggests that a microtubular system–dependent, colchicine‐sensitive transcellular pathway may transport both classes of these ligands. The relationship of this pathway to flux rates, however, remains unclear. Some structural evidence suggests an important role for a Golgi‐associated vesicular system. Monensin, like colchicine, is a perturbing agent that is believed to target primarily Golgi and related organelles. The effects of a minimal effective dose of both colchicine (0.06 mg to 0.12 mg/100 gm body wt) and monensin (0.6 mg/100 gm body wt) were examined in the isolated perfused rat liver in a single‐pass mode. The nonbile salt cholephile, phenol red, was studied at two doses: 1 nmol and 5 μmol. Sodium taurocholate was studied at three doses: 2 nmol, 1 μmol and 5 μmol. Colchicine affected the transcellular transport for both classes of organic anions equally. Partially inhibitory effects on both anions occurred only at high ligand flux rates. In contrast, monensin greatly impaired the transport of nonbile salt cholephiles but had no influence on transcellular bile salt flux. We conclude that the monensin effect appears to define a distinct transcellular transport pathway for each of the two classes of organic anions. (HEPATOLOGY 1991;14:1–9.)