Biliary transport of cholephilic dyes: evidence for two different pathways

The hepatobiliary transport of three structurally related phthaleins was compared in the rat, and found to differ to a large extent in three experimental conditions: 1) after a 72-h fast; 2) after a 4-day phenobarbital treatment; and 3) during infusion of bile salts: sodium dehydrocholate or taurocholate. In the fasting group, bile flow and bile salt excretion (on a whole liver basis) decreased by 49 and 41%, respectively; bromsulphthalein sodium (BSP) and dibromsulphthalein sodium (DBSP) transport maximum (Tm) were reduced by 59 and 50%; however, rose bengal (RB) Tm remained normal. Phenobarbital pretreatment yielded a 44 and 29% increase in BSP and DBSP Tm, respectively, whereas RB Tm remained unchanged. Dehydrocholate infusion caused a 27 and 49% increase in BSP and DBSP Tm, whereas RB Tm increased by 12%. On the contrary, equimolar taurocholate infusion yielded a more important increase in RB Tm (56%) than in BSP and DBSP (31 and 22% respectively). It is suggested that RB does not share the same liver-to-bile excretory pathway as that of the former molecules. Our results emphasize the difficulties in predicting the biliary excretion of foreign compounds, even when their structure is closely similar.