The progression of renal damage resulting from reduced nephron mass has bee
n extensively studied in the 5/6 nephrectomized rat. However, reabsorption
of small peptides and D-glucose across the renal proximal tubule in this mo
del remains poorly understood. In this study, we examined the alterations o
f H+-peptide cotransporters (PEPT1 and PEPT2) and Na+-D-glucose cotransport
ers (SGLT1 and SGLT2) in chronic renal failure. Two weeks after surgery, H-dependent [C-14] glycylsarcosine uptake by the renal brush-border membrane
vesicles isolated from 5/6 nephrectomized rats was significantly increased
compared with that from sham-operated controls. Kinetic analysis revealed
that the maximum velocity value for [C-14] glycylsarcosine uptake by the hi
gh-affinity-type of peptide transporter was increased threefold by 5/6 neph
rectomy, without significant changes in the apparent Michaelis-Menten const
ant value. Competitive PCR analyses indicated that the expression of PEPT2
mRNA was markedly increased in the remnant kidney, but PEPT1, SGLT1, and SG
LT2 mRNA levels showed no significant changes. These findings indicated tha
t the high-affinity-type H+-peptide cotransport activity is upregulated by
5/6 nephrectomy, accompanied by the increased expression of PEPT2. The upre
gulation of PEPT2 expression would result in an increase in reabsorption of
small peptides and peptide-like drugs across the brush-border membranes in
chronic renal failure.