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      Effects of ATP and UTP on [Ca 2+] i, Membrane Potential and Force in Isolated Rat Small Arteries

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          Abstract

          We have investigated excitation-contraction coupling mechanisms associated with the activation of purinoceptors and putative pyrimidinoceptors by assessing the effects of ATP and UTP on cytoplasmic Ca<sup>2+</sup> activity ([Ca<sup>2+</sup>]<sub>i</sub>), membrane potential (E<sub>m</sub>) and force in rat mesenteric small arteries. UTP induced a sustained concentration-dependent contractions, closely associated with concentration-dependent increases in [Ca<sup>2+</sup>]<sub>i</sub>. Superfusion with 0.1 m M UTP caused a sustained depolarisation of 12 ± 1 mV (SE, n = 8). In Ca<sup>2+</sup>-free medium, the increase in [Ca<sup>2+</sup>]<sub>i</sub> and the contraction obtained with UTP (1 mM)were both transient and were inhibited by prior exposure to noradrenaline (NA). In vessels depolarised with KC1, UTP caused no change in E<sub>m</sub>, but a sustained increase in force and a transient increase in [Ca<sup>2+</sup>]i were induced, leading to an increased force/[Ca<sup>2+</sup>]<sub>i</sub> ratio. Similar effects on [Ca<sup>2+</sup>]<sub>i</sub>, E<sub>m</sub> and force were observed with ATP; but the effect of ATP on force was transient, whereas the effect on [Ca<sup>2+</sup>]<sub>i</sub> and E<sub>m</sub> declined only slowly. There was no cross-tachyphylaxis between the responses to ATP and UTP: in the presence of 1 m <X_Underline>M</X_Underline> of either, the other drug induced contractions in low concentrations, as if they acted through distinct receptors. The results suggest that both UTP and probably ATP release intracellular Ca<sup>2+</sup>, possibly from the stores emptied by NA. The sustained response to UTP appears to be due to an influx of extracellular Ca<sup>2+</sup>. UTP but not ATP was found to enhance the force-generating effect of [Ca<sup>2+</sup>]<sub>i</sub>.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1992
          1992
          23 September 2008
          : 29
          : 5
          : 385-395
          Affiliations
          Danish Biomembrane Centre aBiophysics and bPharmacology Institutes, Aarhus University, Aarhus, Denmark
          Article
          158955 J Vasc Res 1992;29:385–395
          10.1159/000158955
          1330018
          626f0f25-8c72-4577-b4ab-96f5a178201c
          © 1992 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.

          History
          : 31 March 1991
          : 30 June 1992
          Page count
          Pages: 11
          Categories
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Purinoceptors,UTP,Membrane potential,Intracellular [Ca2+],Small arteries,ATP,Pyrimidinoceptors,Vasoconstriction

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