Hepatocellular uptake of bile acids in the dog: Evidence for a common carrier-mediated transport system. An indicator dilution study.
The purpose of this study was to compare the uptake of taurocholate (TC) by the liver of the dog to that of taurochenodeoxycholate (TCDC) and to examine the influence of TCDC on TC uptake. The uptake of these bile acids by the liver of the intact was studied with the multiple indicator dilution method, using 51Cr-labeled red blood cells as a vascular indicator, 125I-labeled albumin as an extravascular reference, and one or two labeled bile acids. The analysis of the dilution curves fitted well a three-compartment model, and no return of the extracted bile acids to the extracellular space could be detected. The initial space of distributin of TC in the presence of a fixed dose of TCDC was 1.25 +/- 0.09 (SD) times greater than that of albumin. Analysis of the data for TC uptake in the presence of TCDC was consistent with Michaelis-Menten kinetics, as previously established for TC alone. The calculated initial maximal velocity of uptake (Vmax) of TC in the precence of TCDC was 4.92 +/- 1.36 (SD) mumoles per sec per 100 g of liver. This value is not significantly different from the Vmax previously calculated for TC alone. The apparent KD (dose of TC yielding half-maximal velocity) was 18.10 +/- 6.14 (SD) mumoles per 100 g of liver, a value significantly higher than that obtained in the absence of TCDC. A K1 (the Michaelis-type constant characterizing the inhibition of TC uptake by TCDC) of 2.71 +/- 1.08 (SD) mumoles of TCDC per 100 g of liver was calculated. These observations are consistent with competitive inhibition of TC uptake by TCDC, and thus with the existence of a common carrier-mediated transport system for TC and TCDC. Estimation of the kinetic characteristics of the two bile acids from dilution curves obtained simultaneously showed that the affinity for the carrier was higher for TCDC than for TC, but that the maximal capacity was lower for TCDC than for TC.
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001667:Binding, Competitive; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D004285:Dogs; D007201:Indicator Dilution Techniques; D008099:Liver / Q000378:metabolism*; D013656:Taurocholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D013656:Taurocholic Acid