AJP - Gastrointestinal and Liver Physiology, Vol 256, Issue 2 312-G318, Copyright © 1989 by American Physiological Society
Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake
J. Cotting, T. Zysset and J. Reichen
Department of Clinical Pharmacology, University of Berne, Switzerland.
To study immediate events during extrahepatic cholestasis, we investigated
the effect of short-term biliary obstruction on the bioelectrical
sinusoidal-canalicular barrier in the rat using molecular weight-matched
uncharged and negatively charged inert solute pairs. The bioelectrical
barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair
carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a
20-min biliary obstruction both decreased by 61 and 11%, respectively, but
only the large molecular weight pair (the inulins) returned to base line
after release of the obstruction. Inert solute clearances were increased
after short biliary obstruction depending on molecular size and negative
charge (ferrocyanide greater than sucrose greater than carboxyinulin
greater than inulin), suggesting that both permeability and bioelectrical
barriers were affected by obstruction. The hepatic extraction in vivo of a
passively transported drug not excreted into bile (D-propranolol) was not
affected by obstruction, whereas that of an actively transported drug
(glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary
obstruction (P less than 0.01). Unidirectional transfer of glycocholate was
not affected by short-term biliary obstruction in the situ perfused rat
liver; however, 2 min after [14C]glycocholate administration, increased
return was observed in hepatic venous effluent in obstructed animals. Our
findings demonstrate a loss of the bioelectrical barrier immediately after
short-term biliary obstruction. Decreased hepatic extraction in the view of
unaltered sinusoidal uptake demonstrates regurgitation of bile into blood
during short-term biliary obstruction.
