AJP - Renal Physiology, Vol 251, Issue 4 619-F626, Copyright © 1986 by American Physiological Society
Dependence of proximal tubule p-aminohippurate secretion on serum proteins and metabolic substrates
D. E. Webb, R. M. Edwards and J. J. Grantham
Renal proximal tubules secrete p-aminohippurate (PAH) and other endogenous
anionic metabolites into the urine. The extent to which organic anion
excretion is regulated is unknown, but recent studies indicate that
peritubular serum proteins may have a role. We determined the relative
effects of serum proteins and metabolic substrates (citrate, lactate, and
alanine) on net PAH secretion in isolated perfused rabbit S2 proximal
tubules. Net PAH secretion was calculated from the bath-to-lumen flux of
[3H]PAH and the isotope specific activity. We corrected the flux for the
important difference in PAH binding between rabbit serum proteins and
bovine serum albumin (BSA); rabbit serum proteins (5.7 g/dl) and BSA (6
g/dl) bound 10 microM PAH 21 and 37%, respectively. BSA had no effect, but
rabbit serum proteins reversibly inhibited PAH secretion in the presence of
metabolic substrates in the bath (40.8%), the perfusate (42.6%), and both
media (31.5%). In the absence of metabolic substrates, rabbit serum
proteins decreased PAH secretion by only 16.8%. PAH secretion was inhibited
by 1 g/dl rabbit serum proteins as effectively as 5.7 g/dl (30.3 and 31.5%,
respectively), indicating that PAH transport is very sensitive to
inhibition by rabbit serum proteins. In the absence of rabbit serum
proteins, metabolic substrates in the bath had no effect on PAH secretion.
We conclude that rabbit serum proteins inhibit basolateral membrane
transport of PAH in proximal tubules. Inhibition by serum proteins is
enhanced by bath or lumen citrate, alanine, and lactate, suggesting that
peritubular plasma proteins and tubule cell metabolism may interact to
modulate proximal tubule organic anion secretion and urinary excretion.
