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      Protein Kinase C Mechanism Enhances Vascular Muscle Relaxation by the Ca 2+ Antagonist, Ro 40-5967


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          Actions of the novel Ca<sup>2+</sup> antagonist, Ro 40-5967, which displays unusual efficacy against endothelin (ET)-induced contractions, were studied in isolated vascular muscle cells (VMCs) using the fluorescent protein kinase C (PKC) indicator, BODIPY 12α-phorbol ester-13β-acetate (PBA-BODIPY). High-sensitivity (photon-counting) digital-imaging microscopy quantified PKC distribution within VMCs and showed translocation from the cytosol to the cell surface membrane on stimulation with ET. ET (1 nM) stimulated translocation of PBA-BODIPY fluorescence that peaked at 4 min, increasing from 19 ± 2% to 29 ± 2% surface membrane (edge) distribution (n = 44, p < 0.05). Increases in membrane-associated PKC due to translocation began within 2 min and persisted for about 10 min, after which a gradual decline to control levels occurred. Upon exposure to Ro 40-5967 (10 µM), there was an inhibition of fluorescence intensity throughout the cell. Average fluorescence intensity decreased to 84 ± 4% (n = 20, p < 0.05) of that in prestimulus controls. Cell/membrane was also reduced to below unstimulated control levels. Amlodipine failed to decrease PKC fluorescence intensity or translocation to the surface membrane. These data suggest that there is an important direct PKC inhibitory action of Ro 40-5967 that would at least partially explain relaxation of ET-induced contractions.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 33
          : 1
          : 71-77
          Oregon Regional Primate Research Center and Departments of Medicine and Cell and Developmental Biology, Oregon Health Sciences University, Beaverton, Oreg., USA
          159134 J Vasc Res 1996;33:71–77
          © 1996 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.

          : 19 May 1995
          : 08 August 1995
          Page count
          Pages: 7
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Mibefradil,Digital imaging microscopy,Inhibition,Vasodilator,PKC translocation,Amlodipine,Endothelin


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