Fleischer A B, Shurmantine W O, Thompson F L, Forker E L, Luxon B A
J Lab Clin Med. 1985 Feb;105(2):185-9.
Organic anions destined for hepatic uptake often bind to albumin in the circulation. Because albumin binds to liver cells but is not transported, we suggest that sites on the hepatocyte surface catalyze the dissociation of albumin-anion complexes, thus making more free anion available for transport than would otherwise occur. To learn whether liver cells distinguish between free albumin and albumin-anion complexes, we measured the binding of 125I-albumin to isolated rat hepatocytes in the presence and absence of rose bengal, a transported anion that binds extensively to albumin. Albumin binding to hepatocytes is reported as the albumin space corrected for extracellular fluid (14C-inulin space). Corrected albumin spaces are 2.95 and 2.83 microliter/mg cell protein with and without rose bengal, respectively. The mean difference and its 95% confidence interval computed from four comparisons in each of six rats is 0.12 +/- 0.67 microliter/mg cell protein. Inulin space is 32% of the uncorrected albumin space. Thus the affinities of albumin-rose bengal complexes and of free albumin for the hepatocyte surface differ by at most 28%. Accordingly, free albumin can compete with albumin-rose bengal complexes for cell surface sites, impairing the surface-mediated generation of free rose bengal for uptake. This finding explains the otherwise paradoxical observation that adding albumin to liver perfusate inhibits the uptake of rose bengal even when sufficient albumin is already present to bind 99.9% of this dye.
destined for hepatic uptake often bind to albumin in the circulation. Because albumin binds to liver cells but is not transported, we suggest that sites on the hepatocyte surface catalyze the dissociation of albumin-anion complexes, thus making more free anion available for transport than would otherwise occur. To learn whether liver cells distinguish between free albumin and albumin-anion complexes, we measured the binding of 125I-albumin to isolated rat hepatocytes in the presence and absence of rose bengal, a transported anion that binds extensively to albumin. Albumin binding to hepatocytes is reported as the albumin space corrected for extracellular fluid (14C-inulin space). Corrected albumin spaces are 2.95 and 2.83 microliter/mg cell protein with and without rose bengal, respectively. The mean difference and its 95% confidence interval computed from four comparisons in each of six rats is 0.12 +/- 0.67 microliter/mg cell protein. Inulin space is 32% of the uncorrected albumin space. Thus the affinities of albumin-rose bengal complexes and of free albumin for the hepatocyte surface differ by at most 28%. Accordingly, free albumin can compete with albumin-rose bengal complexes for cell surface sites, impairing the surface-mediated generation of free rose bengal for uptake. This finding explains the otherwise paradoxical observation that adding albumin to liver perfusate inhibits the uptake of rose bengal even when sufficient albumin is already present to bind 99.9% of this dye.
注定要被肝脏摄取的有机阴离子通常在循环中与白蛋白结合。由于白蛋白与肝细胞结合但不被转运，我们认为肝细胞表面的位点催化白蛋白 - 阴离子复合物的解离，从而使更多的游离阴离子可用于转运，否则情况并非如此。为了了解肝细胞是否能区分游离白蛋白和白蛋白 - 阴离子复合物，我们在有和没有孟加拉玫瑰红（一种与白蛋白广泛结合的转运阴离子）存在的情况下，测量了125I - 白蛋白与分离的大鼠肝细胞的结合。白蛋白与肝细胞的结合以校正细胞外液后的白蛋白空间（14C - 菊粉空间）来表示。有和没有孟加拉玫瑰红时，校正后的白蛋白空间分别为2.95和2.83微升/毫克细胞蛋白。从六只大鼠中每只进行的四次比较计算出的平均差异及其95%置信区间为0.12±0.67微升/毫克细胞蛋白。菊粉空间是未校正白蛋白空间的32%。因此，白蛋白 - 孟加拉玫瑰红复合物和游离白蛋白对肝细胞表面的亲和力差异最多为28%。相应地，游离白蛋白可以与白蛋白 - 孟加拉玫瑰红复合物竞争细胞表面位点，损害表面介导的游离孟加拉玫瑰红的生成以供摄取。这一发现解释了一个看似矛盾的观察结果，即向肝脏灌流液中添加白蛋白会抑制孟加拉玫瑰红的摄取，即使已经存在足够的白蛋白来结合99.9%的这种染料。
