Transcellular transport of organic anions in the isolated perfused rat liver: the differential effects of monensin and colchicine.
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 mumol. Sodium taurocholate was studied at three doses: 2 nmol, 1 mumol and 5 mumol. 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.
Aoyama
N
N
Gastrointestinal Research Unit, Cleveland Clinic Foundation, Ohio 44195-5218.
Ohya
T
T
Chandler
K
K
Gresky
S
S
Holzbach
R T
RT
D000818:Animals; D000838:Anions / Q000378:metabolism*; D001692:Biological Transport; D003078:Colchicine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D010477:Perfusion; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000493:pharmacokinetics
D000838:Anions; D013656:Taurocholic Acid; D008985:Monensin; D010637:Phenolsulfonphthalein; D003078:Colchicine