Inhibitory Effects of Nicorandil on Rat Mesangial Cell Proliferation via the Protein Kinase G Pathway

Abstract

We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K_ATP) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 µ M to 1 m M inhibited [³H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 µ M to 1 m M) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3′,5′-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K_ATP mediators. Cromakalim, a K_ATP activator, and glibenclamide, a K_ATP inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.

Journal

Journal ID (publisher-id): NEF

Journal ID (nlm-ta): Nephron

Journal ID (doi): 10.1159/issn.1660-8151

Title: Nephron

Publisher: S. Karger AG

ISSN (Print): 1660-8151

ISSN (Electronic): 2235-3186

Publication date Subscription-year: 2001

Publication date (Print): 2001

Publication date (Electronic): 16 March 2001

Volume: 87

Issue: 3

Pages: 263-268

Affiliations

^aSecond Department of Internal Medicine and ^bDepartment of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Fukuoka, Japan

Article

Publisher ID: 45924 Other ID: Nephron 2001;87:263–268

DOI: 10.1159/000045924

PubMed ID: 11287762

Copyright statement: © 2001 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: 6, References: 25, Pages: 6

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Categories

Subject: Original Paper