Inhibition of Protein Reabsorption in the Renal Proximal Tubule by Basic Amino Acids

Abstract

The effects of basic and neutral amino acids on the reabsorption of ¹²⁵I-lysozyme by the renal proximal tubule were examined in rats. In whole animal experiments control animals were given an intravenous (i.v.) injection of ¹²⁵I-lysozyme alone while experimental animals received an i.v. injection of either a basic or a neutral amino acid prior to the injection of ¹²⁵I-lysozyme. In control animals the renal content of ¹²⁵I-lysozyme 30 min after injection was 35% of the injected dose. After injection of basic amino acids there was a significant decrease in the renal uptake of lysozyme. There was no effect of neutral amino acids on the reabsorption of lysozyme. In microperfusion experiments proximal convoluted tubules were perfused in vivo for 3 min with a solution containing ¹²⁵I-lysozyme and either lysine or alanine. In tubules perfused with lysine there was a significant decrease in the reabsorption of lysozyme, whereas alanine had no effect on lysozyme uptake. Electron microscope autoradiography revealed that lysozyme was located in endocytic vesicles and lysosomes in both experimental groups. However, the autoradiographic grain density was significantly decreased in tubules perfused with lysine as compared with those perfused with alanine. These findings demonstrate that basic amino acids inhibit the reabsorption of the cationic protein lysozyme by the proximal tubule cells.

Characterization of proteinuria and tubular protein uptake in a new model of oral L-lysine administration in rats

“…A number of these proteins were identified by immunoblotting or mass spectrometry including albumin, transferrin, DBP, RBP, b 2 -microglobulin, haptoglobin, hemopexin, and angiotensinogen, several of which are known ligands to the proximal tubule endocytic receptors megalin or cubilin. Intravenously infused L-lysine has been frequently used in order to inhibit tubular uptake of proteins [11][12][13]16 and radiolabeled compounds used in experimental cancer therapy. [6][7][8] The use of intravenous infusion requires venous catheterization limiting the time for which this can be applied.…”

“…[3][4][5][6][7][8][9] Basic amino acids, notably L-lysine, inhibit the reabsorption of proteins in the proximal tubule whereas neutral or acidic amino acids do not. 10,11 Inhibition of proximal tubule endocytosis of plasma proteins and peptides by L-lysine infusion has been evaluated in several experimental studies [12][13][14] primarily based on analysis of the excretion of specific proteins in the urine.…”

Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin

“…To test the possible relevance of these findings in vivo, we used an animal model of acute inhibition of PT megalin-mediated albumin reabsorption obtained by the treatment of BALB/C mice with L-lysine ( Figure 6 A). It is well accepted that treatment with L-lysine inhibits PT albumin endocytosis due to the inhibition of megalin internalization [ 16 , 17 ]. Here, it was observed that mice treated with L-lysine had lower PTEC albumin endocytosis, visualized by decreased BSA-FITC uptake in PTs ( Figure 6 B).…”