Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function
Extracellular purines and pyrimidines (ATP, ADP, UTP and adenosine) are released into the extracellular milieu in response to a variety of stress conditions and act as important regulators of vascular homeostasis. This new book is uniquely focused on the
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Evgenia Gerasimovskaya · Elzbieta Kaczmarek Editors
Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function Implications for Health and Disease
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Editors Dr. Evgenia Gerasimovskaya University of Colorado Denver Department of Pediatrics Critical Care Medicine Pediatric Clinical Services 12700 East 19th Avenue Aurora CO 80045 USA
Dr. Elzbieta Kaczmarek Harvard Medical School Beth Israel Deaconess Medical Center 99 Brookline Ave. Boston MA 02215 USA
ISBN 978-90-481-3434-2 e-ISBN 978-90-481-3435-9 DOI 10.1007/978-90-481-3435-9 Springer Dordrecht Heidelberg London New York Library of Congress Control Number: 2010922800 © Springer Science+Business Media B.V. 2010 No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
Preface
Purine and pyrimidine nucleotides and nucleosides function as components of DNA and RNA, are central in cellular energy metabolism, directly interact with mutliple proteins and participate in over 500 enzymatic reactions including phosphorylations, glycosylations, and phospholipid biosynthesis. Perhaps because of these well studied functions of intracellular purine and pyrimidine compounds, the view of extracellular nucleotides as important signaling molecules that are secreted from both resting and activated cells and exert various autocrine/paracrine effects, was not accepted readily. The breakthrough in the purinergic signaling field was achieved by identification and cloning of the nucleotide targets, P2 purinergic receptors, followed by extensive characterization of two groups of these receptors, P2Y (metabotropic) and P2X (ionotropic). These advances led to numerous studies that elucidated extracellular nucleotide-initiated signaling pathways and their outcomes in different cell types and tissues. Moreover, it is well accepted now that purinergic signaling is regulated by the levels/availability of their specific ligands, which, in turn, depend on the net balance between nucleotide release and their metabolism by nucleotide- and nucleoside- converting ecto-enzymes. One of the cell types frequently exposed to extracellular nucleotides is the endothelium. In addition, endothelial cells themselves release nucleotides, therefore they represent both the source and the target for adenine nucleotides. It is well established that the endothelium plays a central role in regulation of vascular tone and permeability, blood clotting, inflammation, interaction with blood cells and angiogenesis. However, despite the progress in our understanding of purinergic regulation of vascular function, the role of extracellular purines and pyri
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