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      Potential Functional Roles of Extracellular ATP in Kidney and Urinary Tract

      a , a , b

      Cardiorenal Medicine

      S. Karger AG

      Adenosine triphosphate, P2X receptor, P2Y receptor

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          Abstract

          P2 receptors are sensitive to adenosine triphosphate (ATP) and uridine triphosphate and can be divided into two major subtypes: P2X and P2Y receptors. They are specific membrane-bound receptors which when activated by extracellular ATP initiate a variety of biological effects. The P2X receptors are ligand-gated channels, whereas the P2Y receptors are coupled to G proteins linked to second-messenger systems. In this review, the potential functional roles of extracellular ATP in the kidney and lower urinary tract are discussed and briefly explored in the context of some specific renal and urinary tract abnormalities.

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          Most cited references 10

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          A P2X purinoceptor expressed by a subset of sensory neurons.

          ATP is known to depolarize sensory neurons, and may play a role in nociceptor activation when released from damaged tissue. Here we report the molecular cloning and characterization of a new member of the P2X receptor family, P2X3, expressed by these cells. The channel transcript was present in a subset of rat dorsal-root-ganglion sensory neurons, some of which express nociceptor-associated markers; it was absent in other tissues that were tested, including sympathetic, enteric and central nervous system neurons. Moreover, when expressed in Xenopus oocytes, the channel showed an ATP-dependent cation flux. P2X3 is the only ligand-gated channel known to be expressed exclusively by a subset of sensory neurons. The remarkable selectivity of expression of the channel coupled with its sensory neuron-like pharmacology suggests that this channel may transduce ATP-evoked nociceptor activation.
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            Purinoceptors: Are there families of P2X and P2Y purinoceptors?

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              Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation.

              Recovery of cell volume in response to osmotic stress is mediated in part by increases in the Cl- permeability of the plasma membrane. These studies evaluate the hypothesis that ATP release and autocrine stimulation of purinergic (P2) receptors couple increases in cell volume to opening of Cl- channels. In HTC rat hepatoma cells, swelling induced by hypotonic exposure increased membrane Cl- current density to 44.8 +/- 7.1 pA/pF at -80 mV. Both the rate of volume recovery and the increase in Cl- permeability were inhibited in the presence of the ATP hydrolase apyrase (3 units/ml) or by exposure to the P2 receptor blockers suramin and Reactive Blue 2 (10-100 microM). Cell swelling also stimulated release of ATP. Hypotonic exposure increased the concentration of ATP in the effluent of perfused cells by 170 +/- 36 nM in the presence of a nucleotidase inhibitor (P < 0.01). In whole-cell recordings with ATP as the charge carrier, cell swelling increased membrane current density approximately 30-fold to 16.5 +/- 10.4 pA/pF. These findings indicate that increases in cell volume lead to efflux of ATP through opening of a conductive pathway consistent with a channel, and that extracellular ATP is required for recovery from swelling. ATP may function as an autocrine factor that couples increases in cell volume to opening of Cl- channels through stimulation of P2 receptors.
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                Author and article information

                Journal
                EXN
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                1998
                June 1998
                22 May 1998
                : 6
                : 3
                : 200-207
                Affiliations
                a Centre for Nephrology and b Department of Anatomy and Developmental Biology, University College, London, UK
                Article
                20524 Exp Nephrol 1998;6:200–207
                10.1159/000020524
                © 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: 2, References: 62, Pages: 8
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/20524
                Categories
                Minireview

                Cardiovascular Medicine, Nephrology

                P2Y receptor, Adenosine triphosphate, P2X receptor

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