AJP - Renal Physiology, Vol 243, Issue 4 379-F392, Copyright © 1982 by American Physiological Society
Kinetics, competition, and selectivity of tubular absorption of proteins
B. E. Sumpio and T. Maack
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.
