Characterization of the transport system for β-lactam antibiotics and dipeptides in rat renal brush-border membrane vesicles by photoaffinity labeling

Kramer, Werner; Leipe, Irina; Petzoldt, Evelyne; Girbig, Frank

doi:10.1016/0005-2736(88)90059-4

Cited by 28 publications

(3 citation statements)

References 23 publications

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“…The 127-kD protein was identified and characterized by photolabeling experiments with kidney and intestinal BBMV using benzylpenicillin and photoreactive azido analogues of Gly-Pro and cephalexin (17,(19)(20)(21). All three photoprobes labeled the same protein.…”

Section: Discussionmentioning

confidence: 99%

Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter.

Daniel¹,

Adibi²

1993

J. Clin. Invest.

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This study was designed to determine whether ii-lactam antibiotics (cephalosporins and penicillins) are all substrates for the renal oligopeptide/H+ symporter and, if so, whether the transport system discriminates among the numerous #l-lactam antibiotics. We used [3HIglycylglutamine, 13Hlcephalexin, and 13H1-ampicillin as probes for the transport of oligopeptides, cephalosporins, and penicillins in kidney brush border membrane vesicles, respectively. Among the lt-lactam antibiotics, only those with an a-amino group in the phenylacetamido moiety were found to interact with the oligopeptide/H+ symporter.Aminocephalosporins displayed high affinities (Kis generally < 250 ,gM), whereas aminopenicillins displayed low affinities (K; 0.78-3.03 mM). These differences in affinities appeared to be a consequence of conformational features of the substrates, especially the sterical location of the carboxy group. The affinities of aminolactams for the oligopeptide /H + symporter were, furthermore, related to the hydrophobicity of the phenylglycyl chains and the substituents attached to the thiazolidine and dihydrothiazine ring. In sharp contrast to the uptake of 13H1-glycylglutamine and I3Hlcephalexin, the uptake of 13H1-ampicillin was not dependent on a pH gradient and was inhibited by various ,-lactam antibiotics, whether or not they contained an a-amino group. Our data suggest that: (a) the transport of aminocephalosporins is largely mediated by the oligopeptide/H+ symporter, which is highly influenced by the substrate structure; and (b) penicillins are transported by another system, which is less discriminative with respect to substrate structure. (J. Clin. Invest. 1993. 92:2215-2223

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Section: Discussionmentioning

confidence: 99%

Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter.

Daniel¹,

Adibi²

1993

J. Clin. Invest.

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“…Kramer et al5,29–31 performed some of the earliest studies identifying a peptide transporter that is a 127 kDa protein from the brush border membrane of rabbit intestinal and renal epithelial cells 5. This protein presented affinity for di‐ and tripeptides, β‐lactam antibiotics, and renin inhibitors 29–31.…”

Section: Mammalian Oligopeptide Transporters and Isoformsmentioning

confidence: 99%

“…The importance of peptide transporters in helping to increase the transcellular diffusion of peptides and peptide‐based drugs has been well established,4–20 and as a result, several companies have developed strategies to obtain therapeutic agents with a high molecular recognition for these transporters to help increase bioavailability. For instance, the efficient oral absorption of some of these drugs depends on proteins expressed in the small intestine 4,6,9–12,14–19…”

Section: Introductionmentioning

confidence: 99%

Current Perspectives on Established and Putative Mammalian Oligopeptide Transporters

Herrera-Ruiz

Knipp

2003

Journal of Pharmaceutical Sciences

103

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Dipeptide uptake: A novel marker for testicular and ovarian macrophages

Otto¹,

Bauer²

1996

Anat. Rec.

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Background Testicular and ovarian macrophages seem to be involved in paracrine regulation of steroidogenesis. Markers suitable for the identification of these cells under viable conditions would allow new experimental approaches in the study of biological interactions between hormone‐producing cells and tissue macrophages. Methods and results: Dipeptide uptake was studied in primary cultures from rat testis and ovaries with the fluorescent dipeptide derivative β‐Ala‐Lys‐Nϵ‐aminomethylcoumarin acetic acid (AMCA). Fluorescence microscopic studies revealed that the reporter peptide accumulated specifically in testicular macrophages, which were identified by subsequent immunostaining with the OX‐42 antibody. In the ovarian cultures, however, transport of the fluorescence‐labeled dipeptide was observed in cells that exhibited the morphological characteristics of macrophages but did not show positive immunoreactivity against the antibody employed. In both cases, dipeptide accumulation was blocked by the addition of Tyr‐Gly, thus indicating that transport was not due to endocytosis. Competition studies performed with primary cultures from testis have shown that di‐ and tripeptides effectively reduce uptake of the tracer peptide, whereas compounds without an α‐ or β‐amino group, such as captopril and benzylpenicillin, do not. Conclusions These results indicate that the testicular and ovarian macrophages are equipped with a dipeptide transport system. The selective accumulation of the fluorescent dipeptide derivative β‐Ala‐Lys‐Nϵ‐AMCA in testicular and ovarian macrophages permits the identification of these cell types under viable conditions. © 1996 Wiley‐Liss, Inc.

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Characterization of the transport system for β-lactam antibiotics and dipeptides in rat renal brush-border membrane vesicles by photoaffinity labeling

Cited by 28 publications

References 23 publications

Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter.

Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter.

Current Perspectives on Established and Putative Mammalian Oligopeptide Transporters

Dipeptide uptake: A novel marker for testicular and ovarian macrophages

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