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      Effect of Protamine on Cation-Selective Permeability in Hamster Medullary Thick Ascending Limb of Henle’s Loop

      , ,

      Nephron

      S. Karger AG

      Paracellular shunt pathway, Protamine, Renal medulla, Cation permeability

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          Abstract

          To estimate the contribution of the paracellular shunt pathway to cation-selective permeability in the hamster medullary thick ascending limb of Henle’s loop, we observed the effect of protamine, a selective blocker of paracellular conductance, on salt-diffusion voltage (dV<sub>T</sub>) in the isolated nephron segment perfused in vitro. When 300 µg/ml protamine was added to the lumen, the lumen-positive dV<sub>T</sub> generated upon reduction of the lumen NaCl concentration was decreased from 5.1 ± 0.9 to 0.8 ± 0.8 mV and the calculated Na<sup>+</sup>/Cl<sup>–</sup> permeability ratio was decreased from 1.40 ± 0.14 to 0.86 ± 0.08. Although the effect of protamine persisted after removal of the agent from the lumen, addition of 30 U/ml heparin, which neutralizes protamine, returned the dV<sub>T</sub> toward the control level. This effect was almost the same when the orientation of the imposed NaCl gradient was reversed. Protamine exhibited a similar effect on dV<sub>T</sub> in the presence of ouabain added to the bath. Protamine was without effect from the bath. Protamine did not affect the basel V<sub>T</sub> perfused with the control solution. Increased V<sub>T</sub> by decreasing perfusion pressure was inhibited by adding protamine from the lumen. These observations suggest that the paracellular pathway contributes to the cation selectivity of the medullary thick ascending limb. The cation selectivity of the paracellular shunt pathway may mainly account for the changes in V<sub>T</sub> which are either dependent on the luminal flow rate or transmural NaCl concentration gradient, while it may not contribute to the basal level of V<sub>T</sub>.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1998
          April 1998
          26 March 1998
          : 78
          : 4
          : 474-480
          Affiliations
          Department of Pharmacology, Jichi Medical School, Tochigi, Japan
          Article
          44977 Nephron 1998;78:474–480
          10.1159/000044977
          9578074
          © 1998 S. Karger AG, Basel

          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: 3, Tables: 6, References: 23, Pages: 7
          Product
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/44977
          Categories
          Original Paper

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