Kinetics, competition, and selectivity of tubular absorption of proteins. Academic Article uri icon

Overview

abstract

  • Tubular absorption (T) of two cationic proteins, lysozyme (LZM) and cytochrome c (CYT c), and two anionic proteins, beta 2-microglobulin (beta 2M) and 125I-labeled human growth hormone (hGH), was studied in the isolated perfused rat kidney. All four proteins are extensively filtered and, at low loads, almost completely absorbed by the tubular epithelium. TLZM and TCYT c is a saturable process of high capacity (Tm) and low apparent affinity. (Tm)LZM was two orders of magnitude larger than (Tm)CYT c. LZM inhibited TCYT c in a dose-dependent and reversible manner. Saturating loads of CYT c failed to inhibit T beta 2M and ThGH. Saturation, selectivity, and competition is explained on the basis of a model that incorporates adsorption of protein to microvilli as well as geometric and electrical constraints on the access of filtered proteins to endocytic sites at the base of the microvilli. Tubular absorption of all proteins is decreased by inhibitors of the formation and/or internalization of endocytic vesicles (iodoacetate and cytochalasin B). However, lysine (5 mM) and low perfusate calcium concentration (0.5 mM) inhibited T beta 2M but not TCYT c and ThGH. The selective effect of 5 mM lysine, which causes morphologic damage in initial portions of the proximal convoluted tubule, may be due to preferential or exclusive absorption of beta 2 M in this portion of the nephron. The results as a whole demonstrate that in addition to net charge other structural features of the protein molecule and of the luminal wall of proximal tubules may be important determinants of the efficiency and capacity of the tubular absorption of filtered proteins.

publication date

  • October 1, 1982

Research

keywords

  • Kidney Tubules
  • Proteins

Identity

Scopus Document Identifier

  • 0020199642

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.1982.243.4.F379

PubMed ID

  • 7124951

Additional Document Info

volume

  • 243

issue

  • 4