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Articles in PresS, published online ahead of print August 21, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.0346.2000
Submitted on January 5, 2001
Accepted on July 30, 2001
1 Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan
2 Department of Laboratory Medicine, University of Tokushima, School of Medicine, Kuramoto-cho, Tokushima 770-8503, Japan
* To whom correspondence should be addressed. E-mail: inui{at}kuhp.kyoto-u.ac.jp.
The progression of renal damage resulting from reduced nephron mass has been extensively studied in the 5/6 nephrectomized rat. However, reabsorption of small peptides and D-glucose across the renal proximal tubule in this model remains poorly understood. In this study, we examined the alterations of H+/peptide transporters (PEPT1 and PEPT2) and Na+/D-glucose transporters (SGLT1 and SGLT2) in chronic renal failure. Two weeks after surgery, H+-dependent [14C]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 Vmax value for [14C]glycylsarcosine uptake by the high affinity type of peptide transporter was increased threefold by 5/6 nephrectomy, without significant changes in the apparent Km value. Competitive PCR analyses indicated that the expression of PEPT2 mRNA was markedly increased in the remnant kidney, but PEPT1, SGLT1 and SGLT2 mRNA levels showed no significant changes. These findings indicated that the high affinity type H+/peptide cotransport activity is up-regulated by 5/6 nephrectomy, accompanied by the increased expression of PEPT2. The up-regulation 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.
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