The histoautoradiographic localization of taurocholate in rat liver after bile duct ligation. Evidence for ongoing secretion and reabsorption processes.
To determine whether in complete obstructive cholestasis taurocholate is taken up by hepatocytes and if so whether it is secreted into bile, tritium-labelled taurocholate was localized by histoautoradiography on cryoslices from normal rat livers and from those after bile duct ligation. In non-cholestatic livers the hepatocytes of acinar zones 1 as well as the lumina and the epithelia of bile ductules and ducts became intensely labelled directly after injection of [3H]taurocholate into a mesenterial vein. Four hours and 4 days after bile duct ligation, hepatocytes of all three acinar zones became labelled, but in contrast to the normal state, pericanalicular concentration of silver grains was not observed, not even within 5 min. Fifteen days after bile duct obstruction, cryoslices taken 2 min after injection of [3H]taurocholate exhibited an intense silver grain labelling of all acinar zones, with the highest density at bile canalicular areas of the liver cell plates as well as the proliferated bile ductules and bile ducts. The biliary epithelium of small bile ductules and ducts of non-cholestatic and of bile duct-obstructed livers were also covered with silver grains; the epithelium of larger ducts exhibited significant labelling predominantly at the lateral sites of the cells. The biliary epithelium of the common bile duct was not significantly labelled. The results indicate that in complete obstructive cholestasis (a) taurocholate continues to be taken up from blood by hepatocytes and secreted into bile, but in terms of varying duration of obstruction, (b) all acinar zones are involved in bile salt transport, (c) in the initial phase (4 h and 4 days respectively after bile duct obstruction) hepatocytes fail to concentrate taurocholate at the canalicular site, (d) in a consecutive phase, in which bile ductules and ducts proliferate (demonstrated for a 15-day cholestasis), the taurocholate concentration at the canalicular site of hepatocytes is re-established and biliary secretion seems to be enhanced, (e) the biliary epithelium of bile ductules and ducts may play a significant role in the reabsorption and/or regurgitation of bile salts from bile to blood. Reabsorption/regurgitation of biliary constituents may also be operative in the non-cholestatic state but may become significantly enhanced with bile ductular proliferation.
Buscher
H P
HP
Medizinische Klinik der Universität Freiburg, F.R.G.
Miltenberger
C
C
MacNelly
S
S
Gerok
W
W
D000818:Animals; D001345:Autoradiography; D001652:Bile Ducts; D002779:Cholestasis / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000032:analysis*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000032:analysis* / Q000378:metabolism
D013656:Taurocholic Acid