INFLUENCE OF BACKWARD PERFUSION ON URSODEOXYCHOLATE-INDUCED CHOLERESIS IN ISOLATED INSITU RAT-LIVER

Ursodeoxycholate-induced bicarbonate-rich hypercholeresis was studied in isolated in situ forward- or backward-perfused rat livers. Both spontaneous bile flow and bile acid secretion were similar regardless of the direction of the perfusion. The cholereric effect of tauroursodeoxycholate infusion (400 nmol · min-1 · 100 g-1 body weight) was not significantly different in forward- or backward-perfused livers either. Ursodeoxycholate infusions at low rate (800 nmol · min-1 · 100 g-1 body weight) induced similar bile flow, bile acid output and bicarbonate output in both forward- and backward-perfused livers. Net ursodeoxycholate uptake, measured as [14C]ursodeoxycholate uptake over the bile acid infusion period (30 min), was not significantly different during forward- or backward-perfusion (4.8 and 5.1 μmol/g liver, respectively); i.e., approx. 67% of infused dose (≈7.5 μmol/g liver per 30 min). A 2-fold increase in the dose of ursodeoxycholate infusion (1600 nmol · min-1 · 100 g-1 b.wt.) induced additional enhancement in both bile flow and bicarbonate biliary secretion, but not in bile acid uptake or output, in forward-perfused livers. Moreover, infusion of the same dose of ursodeoxycholate to backward-perfused livers had a significantly lower choleretic effect (-29%, p < 0.001) even though ursodeoxycholate uptake and biliary output were similar regardless of perfusion direction. Net ursodeoxycholate uptake, was only 2.4μmol/g liver; i.e., approx. 16% of infused dose (≈15 μmol/g liver per 30 min). These findings indicate that a process related with the hepatic microanatomy may be involved in the hypercholeretic response to ursodeoxycholate. These results are also consistent with the existence of a cholehepatic shunt pathway. However, our results suggest that even if cholehepatic shunting exists, the recirculation of unconjugated-ursodeoxycholate back to the sinusoids is not mandatory for ursodeoxycholate-induced bicarbonate-rich choleresis, and we thus conclude that additional mechanism(s) may be operating. © 1990.