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

Article Details

Citation

Terada T, Saito H, Mukai M, Inui K

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

Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11.

PubMed ID
9374833 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AmoxicillinSolute carrier family 15 member 1ProteinHumans
Unknown
Inhibitor
Details
AmoxicillinSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
AmpicillinSolute carrier family 15 member 1ProteinHumans
Unknown
Inhibitor
Details
AmpicillinSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
AzidocillinSolute carrier family 15 member 1ProteinHumans
Unknown
Inhibitor
Details
AzidocillinSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
CefadroxilSolute carrier family 15 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefadroxilSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
CefdinirSolute carrier family 15 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefdinirSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
CefiximeSolute carrier family 15 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefiximeSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
CefradineSolute carrier family 15 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefradineSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
CeftibutenSolute carrier family 15 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
CeftibutenSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
CephalexinSolute carrier family 15 member 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
CephalexinSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
CyclacillinSolute carrier family 15 member 1ProteinHumans
Unknown
Inhibitor
Details
CyclacillinSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details