Biliary excretion of sulfobromophthalein compounds in normal and mutant corriedale sheep. Evidence for a disproportionate transport defect for conjugated sulfobromophthalein
✍ Scribed by James L. Barnhart; Ronald R. Gronwall; Burton Combes
- Publisher
- John Wiley and Sons
- Year
- 1981
- Tongue
- English
- Weight
- 624 KB
- Volume
- 1
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Biliary excretion of dye was evaluated in three normal and one mutant Corriedale sheep (characterized by depressed biliary transport of many organic anions) during infusion of unconjugated sulfobromophthalein (BSP) and its preformed glutathione conjugate (BSP-GSH). Maximal dye excretion rates in bile in normal sheep were higher when BSP-GSH rather than BSP was administered. In confirmation of earlier studies, dye excretion in bile was markedly depressed in the mutant animal. However, movement of unconjugated BSP from liver cells into bile remained relatively intact whereas transport of conjugated BSP compounds was virtually absent. Preservation of unconjugated dye entry into bile suggests the presence of a transport mechanism for unconjugated BSP which is preserved in mutant sheep and is distinct from that involved in BSP-GSH excretory transport. Renal clearance of conjugated BSP compounds was greater than of unconjugated BSP and clearance values were comparable in the normal and mutant sheep. Thus, no excretory defect comparable to that present in liver was identifiable in the kidney.
The hepatic transfer of sulfobromophthalein sodium (BSP) in dogs (1-3), guinea pigs (4,5), rats (4,6,7), sheep (S), and man (2) is characterized by a maximum rate of biliary excretion (Tm) in which the majority of the dye in bile has undergone hepatic conjugation with glutathione. A unique opportunity to investigate further the mechanism of biliary excretion is provided by mutant Corriedale sheep characterized by an inherited defect in the biliary excretion of various organic anions including BSP (9). This mutant is thought to serve as an animal model for the Dubin-Johnson syndrome in man. In the present study, hepatic disposition of dye, when either BSP or its synthesized glutathione conjugate (BSP-GSH)