Effect of Trimethoprim-Sulfamethoxazole on Na ⁺ and K ⁺ Transport Properties in the Rabbit Cortical Collecting Duct Perfused in vitro

Abstract

Background: In this study, the membrane mechanisms of hyperkalemia caused by trimethoprim-sulfamethoxazole (TMP-SMX) combination antibiotics were assessed in the cortical collecting duct (CCD). Methods: We used the microelectrode technique and flux measurements, and examined the effects of TMP and SMX on electrical properties of the apical and basolateral membranes in the rabbit CCD perfused in vitro. Results: TMP in the lumen caused increases in apical membrane voltage, fractional apical membrane resistance (fR_A), and transepithelial resistance (R_T), all effects which were completely inhibited by luminal amiloride, but not by luminal Ba²⁺. The luminal TMP inhibited both net Na⁺ reabsorption and K⁺ secretion in the CCD. TMP in the bath slightly but significantly depolarized transepithelial voltage and basolateral membrane voltage without influencing fR_A or R_T. SMX in the lumen or bath had no effect on barrier voltages or resistances. Conclusion: TMP mainly acts on the apical membrane of the CCD, inhibits the amiloride-sensitive macroscopic Na⁺ conductance in this membrane, and thereby decreases the net driving force for K⁺ exit across the membrane, resulting in an inhibition of K⁺ secretion. SMX in the lumen or bath had no effect on the CCD.

Journal

Journal ID (publisher-id): NEP

Journal ID (nlm-ta): Nephron Physiol

Journal ID (doi): 10.1159/issn.1660-2137

Title: Nephron Physiology

Publisher: S. Karger AG

ISSN (Electronic): 1660-2137

Publication date Subscription-year: 2006

Publication date (Print): February 2006

Publication date (Electronic): 23 February 2006

Volume: 102

Issue: 3-4

Pages: p51-p60

Affiliations

Departments of Nephrologyand Clinical Pharmacology, Jichi Medical School, Minamikawachi, Kawachi, Tochigi, Japan

Article

Publisher ID: 89682 Other ID: Nephron Physiol 2006;102:p51–p60

DOI: 10.1159/000089682

PubMed ID: 16286787

Copyright statement: © 2006 S. Karger AG, Basel

License:

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. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Page count

Figures: 7, Tables: 5, References: 22, Pages: 1

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Categories

Subject: Original Paper