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Vol. 287, Issue 2, 684-690, November 1998
College of Pharmacy and Upjohn Center for Clinical Pharmacology,
The University of Michigan, Ann Arbor, Michigan
Angiotensin converting enzyme (ACE) inhibitors are important
therapeutic agents for treating patients with hypertension and cardiovascular diseases. Although most ACE inhibitors are cleared by
the kidney via glomerular filtration and tubular
secretion, little is known about their reabsorption potential. In
particular, it is believed that while certain ACE inhibitors are
transported by the intestinal peptide transporter (PepT1), these same
compounds do not interact with the renal peptide transporter (PepT2).
In the present study, we examined the interaction of quinapril with the
high-affinity peptide transporter, PepT2. Studies were performed in
rabbit renal brush border membrane vesicles in which the uptake of
[14C]glycylsarcosine (GlySar), at low substrate
concentrations, was examined in the absence and presence of quinapril
(and other ACE inhibitors). We found that quinapril was capable of
cis-inhibiting the uptake of GlySar and in a
concentration-dependent manner. While the
Ki for quinapril (
1 mM) was
several-fold higher than the Km for
GlySar ( 160 µM), the interaction was unique in that inhibition of
PepT2 was of a noncompetitive type. Overall, the data suggest that
quinapril is a low-affinity inhibitor of the renal peptide transporter
and that it binds to a site distinct from that of the GlySar binding site.
This article has been cited by other articles:
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  I. Knutter, C. Wollesky, G. Kottra, M. G. Hahn, W. Fischer, K. Zebisch, R. H. H. Neubert, H. Daniel, and M. Brandsch Transport of Angiotensin-Converting Enzyme Inhibitors by H+/Peptide Transporters Revisited J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 432 - 441. [Abstract] [Full Text] [PDF]
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 H. Shen, D. E. Smith, R. F. Keep, J. Xiang, and F. C. Brosius III Targeted Disruption of the PEPT2 Gene Markedly Reduces Dipeptide Uptake in Choroid Plexus J. Biol. Chem., February 7, 2003; 278(7): 4786 - 4791. [Abstract] [Full Text] [PDF]
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C. Shu, H. Shen, N. S. Teuscher, P. J. Lorenzi, R. F. Keep, and D. E. Smith Role of PEPT2 in Peptide/Mimetic Trafficking at the Blood-Cerebrospinal Fluid Barrier: Studies in Rat Choroid Plexus Epithelial Cells in Primary Culture J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 820 - 829. [Abstract] [Full Text] [PDF]
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 C. Shu, H. Shen, U. Hopfer, and D. E. Smith Mechanism of Intestinal Absorption and Renal Reabsorption of an Orally Active Ace Inhibitor: Uptake and Transport of Fosinopril in Cell Cultures Drug Metab. Dispos., October 1, 2001; 29(10): 1307 - 1315. [Abstract] [Full Text] [PDF]
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N. S. Teuscher, A. Novotny, R. F. Keep, and D. E. Smith Functional Evidence for Presence of PEPT2 in Rat Choroid Plexus: Studies with Glycylsarcosine J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 494 - 499. [Abstract] [Full Text]
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 H. Shen, D. E. Smith, T. Yang, Y. G. Huang, J. B. Schnermann, and F. C. Brosius III Localization of PEPT1 and PEPT2 proton-coupled oligopeptide transporter mRNA and protein in rat kidney Am J Physiol Renal Physiol, May 1, 1999; 276(5): F658 - F665. [Abstract] [Full Text] [PDF]
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