Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding.

Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding.
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白蛋白结合不促进分离的灌注大鼠肝脏中肝胆红素的摄取。

DOI:
10.1172/jci111021
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发表时间:
1983
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Wolkoff,AW
Wolkoff,AW
中科院分区:
--
文献类型:
--
作者:
Stollman,YR;Gartner,U;Theilmann,L;Ohmi,N;Wolkoff,AW

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肝脏摄取胆红素是一个高度特异性的快速过程,其动力学特征表明载体介导。在循环中,胆红素很容易与白蛋白结合,并由肝脏从白蛋白中提取。尽管一些研究表明,胆红素的一小部分未结合的部分与肝细胞相互作用并从循环中去除,但最近的实验被解释为表明与白蛋白的结合促进了配体的摄取。已假设存在白蛋白的肝细胞表面受体。本研究旨在直接检查白蛋白是否促进肝脏对胆红素的摄取以及胆红素的摄取是否依赖于与白蛋白的结合。用无蛋白质的氟碳介质灌注大鼠肝脏,注射后测定单次摄取的 1、10 或 200 nmol [3H]胆红素,作为与 125I-白蛋白、125I-配体或仅与[14C]蔗糖参考的等摩尔复合物。注射125I-白蛋白时,10 nmol [3H]胆红素的摄取量为剂量的67.5 +/- 3.7%,注射125I-配体素时为67.4 +/- 6.5%,注射[14C]蔗糖时为74.9 +/- 2.4%(P大于0.1)。在 200 nmol 时,注射的 [3H] 胆红素的摄取降至 46.4 +/- 3.1%(125I-白蛋白)和 63.3 +/- 3.4% [( 14C]蔗糖)(P 小于 0.01),这表明摄取机制已饱和。当用Goresky模型对流入量进行定量时,得到了类似的结果。当[3H]胆红素与等摩尔125I-白蛋白和[14C]蔗糖参考同时注射时,与[14C]蔗糖相比,125I-白蛋白转运没有延迟。这表明白蛋白从假定的肝细胞受体的解离速率必须非常快,这对于高亲和力受体-配体相互作用来说是不寻常的。没有证据表明胆红素通过与白蛋白结合而促进摄取,或白蛋白与肝细胞表面受体相互作用。这些结果表明,肝胆红素摄取机制是一种高亲和力的机制,可以从白蛋白、配体蛋白或碳氟化合物等循环载体中提取胆红素。
Bilirubin uptake by the liver is a rapid process of high specificity that has kinetic characteristics which suggest carrier-mediation. In the circulation, bilirubin is readily bound to albumin, from which it is extracted by the liver. Although several studies suggested that it is the small, unbound fraction of bilirubin which interacts with hepatocytes and is removed from the circulation, recent experiments have been interpreted as suggesting that binding to albumin facilitates ligand uptake. A liver cell surface receptor for albumin has been postulated. The present study was designed to examine directly whether albumin facilitates the hepatic uptake of bilirubin and whether uptake of bilirubin depends on binding to albumin. Rat liver was perfused with a protein-free fluorocarbon medium, and single-pass uptake of 1, 10, or 200 nmol of [3H]bilirubin was determined after injection as an equimolar complex with 125I-albumin, with 125I-ligandin, or free with only a [14C]sucrose reference. Uptake of 10 nmol of [3H]bilirubin was 67.5 +/- 3.7% of the dose when injected with 125I-albumin, 67.4 +/- 6.5% when injected with 125I-ligandin, and 74.9 +/- 2.4% when injected with [14C]sucrose (P greater than 0.1). At 200 nmol, uptake fell to 46.4 +/- 3.1% (125I-albumin) and 63.3 +/- 3.4% [( 14C]sucrose) of injected [3H]bilirubin (P less than 0.01), which suggests saturation of the uptake mechanism. When influx was quantitated by the model of Goresky, similar results were obtained. When [3H]bilirubin was injected simultaneously with equimolar 125I-albumin and a [14C]sucrose reference, there was no delay in 125I-albumin transit as compared with that of [14C]sucrose. This suggested that the off-rate of albumin from a putative hepatocyte receptor would have to be very rapid, which is unusual for high affinity receptor-ligand interaction. There was no evidence for facilitation of bilirubin uptake by binding to albumin or for interaction of albumin with a liver cell surface receptor. These results suggest that the hepatic bilirubin uptake mechanism is one of high affinity which can extract bilirubin from circulating carriers such as albumin, ligandin, or fluorocarbon.
胆红素与人血清白蛋白结合的动力学和机制。
DOI: --
发表时间: 1978
影响因子: 4.8
作者:
R. Gray;S. Stroupe
通讯作者: S. Stroupe
白蛋白对未结合胆红素血管外分布的影响。
DOI: --
发表时间: 1973
期刊: Clinical science and molecular medicine
影响因子: --
作者:
Joseph R. Bloomer;Paul D. Berk;J. Vergalla;Nathaniel I. Berlin
通讯作者: Nathaniel I. Berlin
白蛋白对肝脏摄取未结合胆红素的影响。
DOI: --
发表时间: 1973
期刊: Clinical science and molecular medicine
影响因子: --
作者:
Joseph R. Bloomer;Paul D. Berk;J. Vergalla;Nathaniel I. Berlin
通讯作者: Nathaniel I. Berlin
萘芬诺平对离体灌注大鼠肝脏摄取胆红素和磺溴酞的影响。
DOI: --
发表时间: 1982
期刊: Gastroenterology
影响因子: 29.4
作者:
Gartner,U;Stockert,RJ;Levine,WG;Wolkoff,AW
通讯作者: Wolkoff,AW
DOI: 10.1126/science.6258226
发表时间: 1981-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
WEISIGER, R;GOLLAN, J;OCKNER, R
通讯作者: OCKNER, R