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      Effect of Morphine on Renomedullary Interstitial Cell Proliferation and Matrix Accumulation

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          Abstract

          Renal interstitial scarring is an important feature of heroin-associated nephropathy. We studied the effect of morphine, an active metabolite of heroin, on cultured rat renal medullary interstitial cell (RMIC) proliferation and matrix accumulation. Morphine (10<sup>-12</sup> M) enhanced (p < 0.001) the proliferation of RMIC (control, 15.0 ± 0.5 vs. morphine, 20.4 ± 1.1 × 10<sup>4</sup> cells/ml). This effect of morphine was dose and time dependent. [<sup>3</sup>H]thymidine and bromodeoxyuridine incorporation studies confirmed the mitogenic effect of morphine on RMIC. Morphine also enhanced mRNA expression for c-jun and c-myc on RMIC. However, nalbuphine, a non-addicting alkaloid did not modulate the proliferation of RMIC. Morphine enhanced the accumulation of collagen type I in a dose-dependent manner and also increased (p < 0.001) the accumulation of collagen type III at a high concentration (control, 1,291 ± 55.8 vs. morphine, 10<sup>-4</sup> M, 2,697.6 ± 257.8 ng/μg protein). Morphine did not modulate the accumulation of laminin or fibronectin. Neutralizing antibody to IL·6 inhibited the effect of morphine on RMIC. H7, a protein kinase C inhibitor, also attenuated the morphine-induced RMIC proliferation. The present study provides a basis for a hypothesis that morphine may be playing a role in the development of renal interstitial pathology in patients with heroin addiction.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1997
          1997
          23 December 2008
          : 77
          : 2
          : 225-234
          Affiliations
          Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, N.Y., and The Long Island Campus for Albert Einstein College of Medicine, Bronx, N.Y., USA
          Article
          190277 Nephron 1997;77:225–234
          10.1159/000190277
          9346391
          © 1997 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
          Pages: 10
          Categories
          Original Paper

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