Cellular Physiology and Biochemistry
Original Paper
Interactions of Benzylpenicillin and Non-steroidal Anti-inflammatory Drugs with the Sodium-dependent Dicarboxylate Transporter NaDC-3Burckhardt B.C.1 · Lorenz J.1 · Burckhardt G.1 · Steffgen J.1,21Zentrum Physiologie und Pathophysiologie, Abteilung Vegetative Physiologie und Pathophysiologie, 2Zentrum Innere Medizin, Abteilung Nephrologie und Rheumatologie, Georg-August-Universität Göttingen
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Article / Publication Details
Published online: August 12, 2004
Issue release date: August 2004
Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0
ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)
For additional information: https://www.karger.com/CPB
Abstract
Sodium-dependent dicarboxylate transporters located in the basolateral membrane (NaDC-3) of renal proximal tubule cells maintain the driving force for exchange of organic anions and drugs against α-ketoglutarate via organic anion transporters OAT1 and OAT3. So far, information on direct interaction of drugs with the cloned NaDC-3 was missing. Here we tested the interaction of non-steroidal anti-inflammatory drugs (NSAIDs) and benzylpenicillin with NaDC-3 cloned from winter flounder (fNaDC-3) and human (hNaDC-3) kidneys. Flufenamate and benzylpenicillin inhibited [14C]succinate uptake in oocytes expressing fNaDC-3. Flufenamate elicited Na+-dependent currents in oocytes expressing fNaDC-3 with a reversal potential around -60 mV. Raising extracellular K+ concentration depolarized fNaDC3-expressing oocytes more in the presence of flufenamate than in its absence, an effect not seen with water-injected control oocytes. These findings suggest that flufenamate via interaction with fNaDC-3 increased the K+ conductance. Acetylsalicylate, indomethacin, and salicylate showed small potential-dependent inward currents in fNaDC-3 but not in hNaDC-3 expressing oocytes. Benzylpenicillin induced voltage-dependent inward currents which were Na+-dependent in oocytes expressing fNaDC-3. The currents were, however, much smaller than those induced by succinate, reflecting probably a low fit of the monovalent benzylpenicillin to the dicarboxylate binding site. The data show hitherto unknown effects of monovalent anionic drugs on a transporter for divalent di- and tricarboxylates.
© 2004 S. Karger AG, Basel
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Article / Publication Details
Published online: August 12, 2004
Issue release date: August 2004
Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0
ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)
For additional information: https://www.karger.com/CPB
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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