Enhancement of Na+-dependent bile acid uptake by albumin: direct demonstration in rat basolateral liver plasma membrane vesicles.

The effects of albumin on taurocholate uptake by rat basolateral liver plasma membrane vesicles were examined. With this system direct effects on carrier-mediated Na+-dependent bile acid uptake may be distinguished from nonspecific alterations in carrier-independent diffusion. Bovine serum albumin increased both the initial velocity and peak uptake of taurocholate in the presence of an Na+ gradient but did not enhance Na+-independent bile acid uptake. The effects of albumin were strikingly dependent on albumin concentration. Maximal enhancement of bile acid uptake was observed at albumin concentrations of 0.125 g/dl (18 microM) to 0.25 g/dl (37 microM), which are similar to reported values for the Kd for albumin binding to the plasma membrane. At high albumin concentrations (2.5 g/dl, 367 microM), uptake was reduced but to a lesser extent than the expected fall in free bile acid concentration. Kinetic studies showed that albumin (0.5 g/dl, 74 microM) reduced the taurocholate Km from 36.5 to 16.1 microM but did not affect Vmax, suggesting that albumin binding may increase the affinity of the bile acid receptor for taurocholate. Bovine gamma-globulin, chicken ovalbumin, and human transferrin did not enhance taurocholate uptake. Control experiments demonstrated that the mechanism of the albumin effect was not dependent on residual albumin-bound calcium and did not involve alteration of the underlying driving forces for bile acid uptake (Na+ gradient). These studies have "unmasked" an enhancing effect on taurocholate uptake by low concentrations of albumin that would not have been readily detected at higher concentrations.