Transcellular transport of organic anions in the isolated perfused rat liver: The differential effects of monensin and colchicine

✍ Scribed by Nankei Aoyama; Toshihide Ohya; Kimberly Chandler; Susan Gresky; R. Thomas Holzbach

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 864 KB
• Volume: 14
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840140102

✦ Synopsis

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 g m 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 pmol.

Sodium taurocholate was studied at three doses: 2 -01, 1 pmol and 5 pmol. 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 199 1; 14: 1-9.)

The mechanism of intracellular transport of bile salts and nonbile salt organic anions is not well defined. Data from Lamri et al. (1) and Crawford et al. (2) suggest that intrahepatic transport of bile salts is associated in some way with vesicles related to the Golgi apparatus and, possibly, to the integrity of the microtubular system. An association between the transport of bile salts with either vesicles or organelles (i.e., Golg apparatus and