Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake.
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.
Cotting
J
J
Department of Clinical Pharmacology, University of Berne, Switzerland.
Zysset
T
T
Reichen
J
J
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002250:Carbon Radioisotopes; D001651:Cholestasis, Extrahepatic / Q000503:physiopathology*; D002860:Chromium Radioisotopes; D004195:Disease Models, Animal; D005295:Ferrocyanides; D006000:Glycocholic Acid / Q000378:metabolism; D007444:Inulin; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013395:Sucrose; D013656:Taurocholic Acid / Q000378:metabolism*; D013667:Technetium; D014316:Tritium
D002250:Carbon Radioisotopes; D002860:Chromium Radioisotopes; D005295:Ferrocyanides; D014316:Tritium; D013395:Sucrose; D013656:Taurocholic Acid; D013667:Technetium; D007444:Inulin; C020354:hexacyanoferrate II; D006000:Glycocholic Acid