THE RENAL UPTAKE OF PROTEINS - A NONSELECTIVE PROCESS IN CONSCIOUS RATS
THE RENAL UPTAKE OF PROTEINS - A NONSELECTIVE PROCESS IN CONSCIOUS RATS
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DOI：
10.1038/ki.1988.163
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发表时间：
1988-08-01
影响因子：
19.6
通讯作者：
LAUWERYS, R
中科院分区：
文献类型：
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作者：
BERNARD, A;AMOR, AO;LAUWERYS, R
通过竞争实验研究了清醒大鼠肾脏对蛋白质重吸收的选择性。这些动物被静脉注射越来越多的蛋白质，这些蛋白质的净电荷和大小范围很广，包括溶菌酶、细胞色素C、金属硫蛋白和β。2-微球蛋白，视黄醇结合蛋白，白蛋白和IgG。同时注射外源性蛋白（人β）的尿排泄。2-微球蛋白，视黄醇结合蛋白，白蛋白和/或蛋清溶菌酶（取决于实验）和大鼠。特异性免疫法检测2-微球蛋白、白蛋白、IgG。结果表明，低分子量的阳离子蛋白和低分子量或高分子量的阴离子蛋白可以相互增加尿排泄量。一些观察结果有力地表明，这些影响是由于肾脏摄取的竞争性抑制。在大多数情况下，这种现象与剂量有关，正如细胞色素C注射所证明的那样，这种现象是短暂的、可重复的和可饱和的。此外，注射的蛋白质诱导管状型蛋白尿，而不管它们的净电荷和大小。在阳离子蛋白的情况下，这一发现排除了肾小球渗透性增强的可能性，这是由于肾小球多阴离子的部分中和，正如硫酸鱼精蛋白所证明的那样，导致肾小球型蛋白尿。这些关于肾脏摄取多种特定蛋白质的相互抑制的定量数据使我们对蛋白质的电荷和大小选择性小管重吸收的概念提出了挑战，并假设通过肾小球过滤的蛋白质被共同的小管内吞位点所吸收，而与它们的物理化学特征无关。beta的能力证明了这一点。2-微球蛋白和IgG抑制溶菌酶的摄取，蛋白质对重吸收位点的亲和力不仅仅与其大小和净正电荷有关。也有证据表明，当高剂量静脉注射蛋白质时，诱导溶酶体酶血症，这很可能反映了刺激的胞吐。
The selectivity of the renal reabsorption of proteins has been investigated by competition experiments in conscious rats. The animals were intravenously injected with increasing doses of proteins over a wide range of net charge and size, including lysozyme, cytochrome C, metallothionein, .beta.2-microglobulin, retinol-binding protein, albumin and IgG. The urinary excretion of exogenous proteins injected concomitantly (human .beta.2-microglobulin, retinol-binding protein, albumin and/or egg white lysozyme depending on the experiment) and of rat .beta.2-microglobulin, albumin and IgG was determined with specific immunoassays. The results show that low molecular weight cationic proteins and low or high molecular weight anionic proteins can increase each other''s urinary excretion. Several observations strongly suggest that these effects result from a competitive inhibition of renal uptake. The phenomenon is dose-related in most cases and, as evidenced by cytochrome C injection, transient, reproducible and saturable. In addition, the injected proteins induce a tubular type proteinuria irrespective of their net charge and size. In the case of cationic proteins, this finding excludes the possibility of an enhanced glomerular permeability due to a partial neutralization of the glomerular polyanion which, as demonstrated with protamine sulfate, entails a glomerular type proteinuria. These quantitative data on the mutual inhibiton of renal uptake of a wide spectrum of specific proteins lead us to challenge the concept of charge- and size-selective tubular reabsorption of proteins, and to postulate that proteins filtered through the glomerular are taken up by common tubular endocytotic sites irrespectively of their physicochemical features. As demonstrated by the ability of .beta.2-microglobulin and IgG to inhibit the uptake of lysozyme, the affinity of a protein for reabsorption sites is not simply related to its size and net positive charge. Evidence is also presented that proteins, when administered intravenously at high doses, induce a lysosomal enzymuria most likely reflecting a stimulated exocytosis.