AJP - Renal Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Am J Physiol Renal Physiol 273: F706-F711, 1997;
0363-6127/97 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Terada, T.
Right arrow Articles by Inui, K.-I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Terada, T.
Right arrow Articles by Inui, K.-I.

AJP - Renal Physiology, Vol 273, Issue 5 706-F711, Copyright © 1997 by American Physiological Society


ARTICLES

Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells

T. Terada, H. Saito, M. Mukai and K. Inui
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.

PEPT1 and PEPT2 are H(+)-coupled peptide transporters expressed preferentially in the intestine and kidney, respectively, which mediate uphill transport of oligopeptides and peptide-like drugs such as beta-lactam antibiotics. In the present study, we have compared the recognition of beta-lactam antibiotics by LLC-PK1 cells stably transfected with PEPT1 or PEPT2 cDNA. Cyclacillin (aminopenicillin) and ceftibuten (anionic cephalosporin without an alpha-amino group) showed potent inhibitory effects on the glycylsarcosine uptake in the PEPT1-expressing cells. Other beta-lactams, such as cephalexin, cefadroxil, and cephradine (aminocephalosporins), inhibited modestly the PEPT1-mediated glycylsarcosine uptake. Except for ceftibuten, these beta-lactams showed much more potent inhibitions on the glycylsarcosine uptake via PEPT2 than via PEPT1. Comparison of the inhibition constant (Ki) values between cefadroxil and cephalexin suggested that the hydroxyl group at the NH2-terminal phenyl ring increased affinity for both PEPT1 and PEPT2. It is concluded that PEPT2 has a much higher affinity for beta-lactam antibiotics having an alpha-amino group than PEPT1 and that substituents at the NH2-terminal side chain of these drugs are involved in the recognition by both peptide transporters.


This article has been cited by other articles:


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. Shimakura, T. Terada, H. Saito, T. Katsura, and K.-i. Inui
Induction of intestinal peptide transporter 1 expression during fasting is mediated via peroxisome proliferator-activated receptor {alpha}
Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G851 - G856.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
M. Tsuda, T. Terada, M. Irie, T. Katsura, A. Niida, K. Tomita, N. Fujii, and K.-i. Inui
Transport Characteristics of a Novel Peptide Transporter 1 Substrate, Antihypotensive Drug Midodrine, and Its Amino Acid Derivatives
J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 455 - 460.
[Abstract] [Full Text] [PDF]


Home page
Pharmacol. Rev.Home page
N. Mizuno, T. Niwa, Y. Yotsumoto, and Y. Sugiyama
Impact of Drug Transporter Studies on Drug Discovery and Development
Pharmacol. Rev., September 1, 2003; 55(3): 425 - 461.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
M. Irie, T. Terada, K. Sawada, H. Saito, and K.-I. Inui
Recognition and Transport Characteristics of Nonpeptidic Compounds by Basolateral Peptide Transporter in Caco-2 Cells
J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 711 - 717.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
T. Terada, K. Sawada, T. Ito, H. Saito, Y. Hashimoto, and K.-I. Inui
Functional expression of novel peptide transporter in renal basolateral membranes
Am J Physiol Renal Physiol, November 1, 2000; 279(5): F851 - F857.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
R. A. M. H. Van Aubel, R. Masereeuw, and F. G. M. Russel
Molecular pharmacology of renal organic anion transporters
Am J Physiol Renal Physiol, August 1, 2000; 279(2): F216 - F232.
[Abstract] [Full Text] [PDF]


Home page
J. Bacteriol.Home page
G. Fang, W. N. Konings, and B. Poolman
Kinetics and Substrate Specificity of Membrane-Reconstituted Peptide Transporter DtpT of Lactococcus lactis
J. Bacteriol., May 1, 2000; 182(9): 2530 - 2535.
[Abstract] [Full Text]


Home page
J. Pharmacol. Exp. Ther.Home page
K. Sawada, T. Terada, H. Saito, Y. Hashimoto, and K.-I. Inui
Recognition of L-Amino Acid Ester Compounds by Rat Peptide Transporters PEPT1 and PEPT2
J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 705 - 709.
[Abstract] [Full Text]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. Terada, K. Sawada, H. Saito, Y. Hashimoto, and K.-I. Inui
Functional characteristics of basolateral peptide transporter in the human intestinal cell line Caco-2
Am J Physiol Gastrointest Liver Physiol, June 1, 1999; 276(6): G1435 - G1441.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
K. Iseki, M. Sugawara, K. Sato, I. Naasani, T. Hayakawa, M. Kobayashi, and K. Miyazaki
Multiplicity of the H+-Dependent Transport Mechanism of Dipeptide and Anionic beta -Lactam Antibiotic Ceftibuten in Rat Intestinal Brush-Border Membrane
J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 66 - 71.
[Abstract] [Full Text]


Home page
Am. J. Physiol. Cell Physiol.Home page
U. Wenzel, D. Diehl, M. Herget, and H. Daniel
Endogenous expression of the renal high-affinity H+-peptide cotransporter in LLC-PK1 cells
Am J Physiol Cell Physiol, December 1, 1998; 275(6): C1573 - C1579.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
K. Takahashi, N. Nakamura, T. Terada, T. Okano, T. Futami, H. Saito, and K.-I. Inui
Interaction of beta -Lactam Antibiotics with H+/Peptide Cotransporters in Rat Renal Brush-Border Membranes
J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 1037 - 1042.
[Abstract] [Full Text]


Home page
J. Biol. Chem.Home page
T. Terada, H. Saito, and K.-i. Inui
Interaction of beta -Lactam Antibiotics with Histidine Residue of Rat H+/Peptide Cotransporters, PEPT1 and PEPT2
J. Biol. Chem., March 6, 1998; 273(10): 5582 - 5585.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online