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.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012395:Rose Bengal / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism; D013329:Structure-Activity Relationship; D013448:Sulfobromophthalein / Q000031:analogs & derivatives / Q000378:metabolism*
D001647:Bile Acids and Salts; D013448:Sulfobromophthalein; D012395:Rose Bengal; D010634:Phenobarbital