AJP - Gastrointestinal and Liver Physiology, Vol 249, Issue 1 48-G57, Copyright © 1985 by American Physiological Society
Characterization of calcium deprivation-induced cholestasis in the perfused rat liver
J. Reichen, F. Berr, M. Le and G. H. Warren
To elucidate the role of calcium in regulation of canalicular bile flow, we
studied biliary sucrose permeability and the transport kinetics of
taurocholate in the in situ perfused rat liver. Calcium deprivation did not
adversely affect viability or ultrastructural appearances of the liver.
Removal of calcium led to initial choleresis followed by cholestasis
dependent on external ionized calcium concentration. Biliary recovery of
[14C]sucrose relative to that of tritiated water was determined by a
biliary multiple-indicator dilution technique. Analysis in terms of
irreversible thermodynamics suggested that biliary permeability to sucrose
increased due to a change in the sieving coefficient from 0.135 to 0.435.
Biliary recovery of taurocholate was significantly (P less than 0.001)
reduced in low-calcium medium (from 79.6 +/- 6.5 to 17.6 +/- 11.8%). This
was not due to a defect in hepatocellular uptake of taurocholate as
determined in the perfused rat liver by a multiple-indicator dilution
technique and in isolated hepatocytes. We conclude that calcium
deprivation-induced cholestasis is characterized by an increased biliary
permeability, a defect in cellular translocation and/or canalicular
secretion of bile salts, and a defect in bile salt-independent bile flow.
