8
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      P2X Receptor Immunoreactivity in Different Arteries from the Femoral, Pulmonary, Cerebral, Coronary and Renal Circulations

      research-article
      ,
      Journal of Vascular Research
      S. Karger AG
      P2X receptors, Artery, Immunohistochemistry, ATP

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The expression of the seven P2X receptor subunits (P2X<sub>1–7</sub>) in the rat vascular system was determined using subtype-selective antibodies. Arteries of different sizes (from arterioles to conduit vessels) from a range of vascular beds were used to give an overview of receptor expression. P2X<sub>1</sub> receptor immunoreactivity was detected in the smooth muscle layer of arteries. The relative level of P2X<sub>1</sub> receptor immunoreactivity was dependent on the size of the artery and the vascular bed; expression was highest in small and medium arteries. P2X<sub>4</sub> receptors were detected in all arteries; once again, the relative level of expression was dependent on the size of the artery and the vascular bed. P2X<sub>5</sub> receptor immunoreactivity was barely detectable in most arteries studied. P2X<sub>7</sub> receptor immunoreactivity was generally punctate and associated with the outer adventitial layer. Immunoreactivity for P2X<sub>2</sub>, P2X<sub>3</sub> and P2X<sub>6</sub> receptors was not detected in arteries. These results demonstrate that arteries express multiple P2X receptor subunits and that there is a heterogeneity in the level of expression. The properties of artery P2X receptors correspond to homomeric P2X<sub>1</sub> receptors, and the function of P2X<sub>4</sub> and P2X<sub>5</sub> receptor subunits in arteries is unclear.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP.

          Extracellular ATP exerts its effects through P2 purinoceptors: these are ligand-gated ion channels (P2x) or G-protein-coupled receptors (P2Y, P2U). ATP at P2x receptors mediates synaptic transmission between neurons and from neurons to smooth muscle, being responsible, for example, for sympathetic vasoconstriction in small arteries and arterioles. We have now cloned a complementary DNA encoding the P2x receptor from rat vas deferens and expressed it in Xenopus oocytes and mammalian cells. ATP activates a cation-selective ion channel with relatively high calcium permeability. Structural predictions suggest that the protein (399 amino acids long) is mostly extracellular and contains only two transmembrane domains plus a pore-forming motif which resembles that of potassium channels. The P2x receptor thus defines a new family of ligand-gated ion channels.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pharmacology of cloned P2X receptors.

            There are seven P2X receptor cDNAs currently known. Six homomeric (P2X1, P2X2, P2X3, P2X4, P2X5, P2X7) and three heteromeric (P2X2/P2X3, P2X4/P2X6, P2X1/P2X5) P2X receptor channels have been characterized in heterologous expression systems. Homomeric P2X1 and P2X3 receptors are readily distinguishable by their rapid desensitization, the agonist action of alpha beta methyleneATP, and the block by 2',3'-O-(2,4,6-trinitrophenyl)-ATP. P2X2 receptors are unique among homomeric forms in their potentiation by low pH. Homomeric P2X4 receptors are much less sensitive to antagonism by suramin and pyridoxal 5-phosphate-6-azo-2',4'-disulfonic acid. Homomeric P2X7 receptors are the only form in which 2',3'-O-(4-benzoylbenzoyl)-ATP is more potent than ATP. The heteromeric P2X2/P2X3 receptor resembles P2X2 in slow desensitization kinetics and potentiation by low pH and is similar to P2X3 with respect to agonism by alpha beta methyleneATP and block by 2',3'-O-(2,4,6-trinitrophenyl)-ATP. Other agonists, antagonists, and ions that can be used to differentiate among the receptors are discussed.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors.

              P2X1 receptors for ATP are ligand-gated cation channels, present on many excitable cells including vas deferens smooth muscle cells. A substantial component of the contractile response of the vas deferens to sympathetic nerve stimulation, which propels sperm into the ejaculate, is mediated through P2X receptors. Here we show that male fertility is reduced by approximately 90% in mice with a targeted deletion of the P2X1 receptor gene. Male mice copulate normally--reduced fertility results from a reduction of sperm in the ejaculate and not from sperm dysfunction. Female mice and heterozygote mice are unaffected. In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists are abolished. These results show that P2X1 receptors are essential for normal male reproductive function and suggest that the development of selective P2X1 receptor antagonists may provide an effective non-hormonal male contraceptive pill. Also, agents that potentiate the actions of ATP at P2X1 receptors may be useful in the treatment of male infertility.
                Bookmark

                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
                2001
                August 2001
                11 July 2001
                : 38
                : 4
                : 332-340
                Affiliations
                Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK
                Article
                51064 J Vasc Res 2001;38:332–340
                10.1159/000051064
                11455204
                3787c43e-49e4-4472-b278-32d004376164
                © 2001 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
                Page count
                Figures: 4, Tables: 1, References: 60, Pages: 9
                Categories
                Research Paper

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                P2X receptors,Artery,ATP,Immunohistochemistry

                Comments

                Comment on this article