AJP - Gastrointestinal and Liver Physiology, Vol 261, Issue 2 305-G311, Copyright © 1991 by American Physiological Society
A novel transcellular transport pathway for non-bile salt cholephilic organic anions
N. Aoyama, H. Tokumo, T. Ohya, K. Chandler and R. T. Holzbach
Gastrointestinal Research Unit, Cleveland Clinic Foundation, Ohio 44195-5218.
Non-bile salt cholephilic organic anions comprise a single class of
nonhomologous ligands having a range of hydrophobicity. Hydrophobicity
enhances the hepatic extraction of cholephiles as well as their
partitioning into secreted biliary lipid particles. When hydrophobicity is
correlated with patterns of biliary excretion for studying transcellular
transport, however, the more hydrophobic probes are unsuitable.
Specifically, with the isolated perfused rat liver technique, the excretory
times for sulfobromophthalein and rose bengal were significantly longer
compared with that for the much more hydrophilic analogue phenol red (PR),
which showed only a single, nearly symmetrical excretory peak at 10 min.
Colchicine affected the apparently well-defined PR pathway only at a
saturation dose (10,000 times the tracer dose). In contrast, the effect of
a different perturbant, monensin, was striking at a tracer dose of PR, but
was less evident at a saturation dose. The combined administration of
colchicine and monensin had no additive inhibitory effect on PR excretion
at tracer doses. At a saturation dose of PR, where monensin is less
inhibiting, however, a significant additive inhibitory effect was
observed.(ABSTRACT TRUNCATED AT 250 WORDS)
