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

Studies with taurine-conjugated bile salts have demonstrated two pathways for hepatocellular delivery of bile salts to bile: a cytosolic, microtubule-independent pathway and a membrane-based, microtubule-dependent pathway. However, a significant portion of circulating bile salts may be unconjugated. To determine whether free bile salts utilize similar pathways, we examined the effect of colchicine on the biliary excretion of intravenously administered cholic acid and taurocholate in intact 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 above but with intravenous infusion of taurocholate at 200 nmol/min - 100 gm beginning 0.75 hr before [C-14]cholic acid/[H-3]taurocholate injection. Depleted/reinfused rats were subjected to biliary diversion for 20 hr before colchicine or lumicolchicine pretreatment, infusion of taurocholate and [C-14]cholic acid/[H-3]taurocholate injection. In each group, biliary excretion of [C-14]taurocholate and [H-3]taurocholate was inhibited equally by colchicine; for peak excretion rates the respective inhibition values were 33% and 35% in basal rats, 63% and 65% in superfused rats, and 74% and 76% in depleted/reinfused rats. Biliary excretion of [C-14]taurocholate occurred consistently later than excretion of [H-3]taurocholate, and maximal rates of excretion were reduced. In contrast, plasma uptake rates of [C-14]cholic acid and [H-3]taurocholate were essentially the same in depleted/reinfused rats. Deconvolution analysis of [C-14]taurocholate vs. [H-3]taurocholate biliary excretion curves revealed no significant differences among experimental groups. We conclude that conversion of [C-14]cholic acid to [C-14]taurocholate slightly retards its biliary excretion and diminishes its peak excretion rate compared with exogenous [H-3]taurocholate. However, there appear to be no other differences in hepatocellular processing of the unconjugated and conjugated bile salts: taurocholate generated in the cytosol or taken up from plasma enters the same intracellular pathways for biliary excretion under different conditions.