MICROTUBULE-DEPENDENT TRANSPORT OF BILE-SALTS THROUGH HEPATOCYTES - CHOLIC VS TAUROCHOLIC ACID

Studies with taurine-conjugated bile salts have demonstrated two pathw ays for hepatocellular delivery of bile salts to bile: a cytosolic, mi crotubule-independent pathway and a membrane-based, microtubule-depend ent pathway. However, a significant portion of circulating bile salts may be unconjugated. To determine whether free bile salts utilize simi lar pathways, we examined the effect of colchicine on the biliary excr etion of intravenously administered cholic acid and taurocholate in in tact rats. Basal rats were pretreated with low-dose colchicine or its inactive isomer, lumicolchicine, 1 hr before placement of intravenous and biliary cannulas and 2.75 hr before intravenous injection of [C-14 ]cholic acid and [H-3]taurocholate. Superfused rats were prepared as a bove but with intravenous infusion of taurocholate at 200 nmol/min - 1 00 gm beginning 0.75 hr before [C-14]cholic acid/[H-3]taurocholate inj ection. Depleted/reinfused rats were subjected to biliary diversion fo r 20 hr before colchicine or lumicolchicine pretreatment, infusion of taurocholate and [C-14]cholic acid/[H-3]taurocholate injection. In eac h group, biliary excretion of [C-14]taurocholate and [H-3]taurocholate was inhibited equally by colchicine; for peak excretion rates the res pective inhibition values were 33% and 35% in basal rats, 63% and 65% in superfused rats, and 74% and 76% in depleted/reinfused rats. Biliar y excretion of [C-14]taurocholate occurred consistently later than exc retion of [H-3]taurocholate, and maximal rates of excretion were reduc ed. In contrast, plasma uptake rates of [C-14]cholic acid and [H-3]tau rocholate were essentially the same in depleted/reinfused rats. Deconv olution analysis of [C-14]taurocholate vs. [H-3]taurocholate biliary e xcretion curves revealed no significant differences among experimental groups. We conclude that conversion of [C-14]cholic acid to [C-14]tau rocholate slightly retards its biliary excretion and diminishes its pe ak excretion rate compared with exogenous [H-3]taurocholate. However, there appear to be no other differences in hepatocellular processing o f the unconjugated and conjugated bile salts: taurocholate generated i n the cytosol or taken up from plasma enters the same intracellular pa thways for biliary excretion under different conditions.