Choleresis and cholestasis produced by infusion of taurocholic acid or taurodehydrocholic acid combined with BSP in the rhesus monkey

Abstract

To study the determinants of BSP Tm in rhesus monkeys, animals with indwelling silastic catheters were infused with sufficient BSP to produce a rising plasma concentration and normal saline or taurocholic acid 3.5 μmol/min, 7.0 μmol/min, or 10.5 μmol/min. BSP Tm was 3.84±0.11 mg/kg/10 min during normal saline infusion, 5.52±0.53 mg/kg/10 min during taurocholic acid 3.5 μmol/min, and 3.58±0.41 mg/kg/10 min with taurodehydrocholic acid 3.5 μmol/min, despite greater bile flow with the latter compound. Higher infusion rates of taurocholic acid inhibited BSP Tm and the proportion of conjugated BSP secreted into bile, as well as bile flow and bile acid secretion. Taurodehydrocholic acid 7.0 μmol/min produced similar but less marked effects. These results indicate that bile flow does not explain the effects of bile acids on BSP Tm and suggest that bile acids exert varying effects on BSP transport or binding in micelles. The cholestasis observed with combined BSP and higher bile acid infusion rates is probably due to inhibition of liver cell intermediary metabolism or to liver cell toxicity.