AJP - Gastrointestinal and Liver Physiology, Vol 260, Issue 1 167-G174, Copyright © 1991 by American Physiological Society
Function of rat hepatocyte tight junctions: studies with bile acid infusions
W. G. Hardison, E. Dalle-Molle, E. Gosink, P. J. Lowe, J. H. Steinbach and Y. Yamaguchi
Department of Medicine, Veterans Administration Medical Center, San Diego 92161.
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)
