Rang and Dale’s Pharmacology Seventh Edition H P Rang, MB BS MA DPhil Hon FBPharmacolS FMedSci FRS Emeritus Professor of Pharmacology, University College London, London, UK M M Dale, MB BCh PhD Senior Teaching Fellow, Department of Pharmacology, University of Oxford, Oxford, UK J M Ritter, DPhil FRCP FBPharmacolS FMedSci Emeritus Professor of Clinical Pharmacology, King’s College London, London, UK R J Flower, PhD DSc FBPharmacolS FMedSci FRS Professor, Biochemical Pharmacology, The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK G Henderson, BSc PhD FBPharmacolS Professor of Pharmacology, University of Bristol, Bristol, UK Churchill Livingstone Front Matter Rang and Dale’s Pharmacology SEVENTH EDITION H P Rang MB BS MA DPhil Hon FBPharmacolS FMedSci FRS Emeritus Professor of Pharmacology, University College London, London, UK M M Dale MB BCh PhD Senior Teaching Fellow, Department of Pharmacology, University of Oxford, Oxford, UK J M Ritter DPhil FRCP FBPharmacolS FMedSci Emeritus Professor of Clinical Pharmacology, King’s College London, London, UK R J Flower PhD DSc FBPharmacolS FMedSci FRS Professor, Biochemical Pharmacology, The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK G Henderson BSc PhD FBPharmacolS Professor of Pharmacology, University of Bristol, Bristol, UK Edinburgh, London, New York, Oxford, Philadelphia, St Louis, Sydney, Toronto 2012 For additional online content visit www.expertconsult.com Cover image shows white blood cells emigrating from blood vessels. The inner surface of blood vessels are lined with endothelial cells which express a protein called PECAM-1 at the junction between cells, and less strongly on the cell body. This protein was labelled red with a fluorescently tagged antibody, and genetic modification was used to make the white blood cells (leukocytes) express green fluorescent protein. These can be seen sticking to the endothelial cells, and beginning to transmigrate through the blood vessel wall in response to an inflammatory stimulus. The image was captured by confocal microscopy with laser excitation of the green and red fluorescent labels. A series of flat images through the vessel were taken, and these slices were reconstructed to make a 3D object. Image generated by S. Nourshagh, A. Woodfin and M. Benoit- Voisin (William Harvey Research Institute, London). Commissioning Editor: Madelene Hyde Development Editor: Alexandra Mortimer Editorial Assistant: Kirsten Lowson Project Manager: Elouise Ball Design: Stewart Larking Illustration Manager: Gillian Richards Illustrator: Richard Tibbitts Marketing Manager(s) (UK/USA): Deborah Watkins/Jason Oberacker Copyright is an imprint of Elsevier Inc. © 2012, Elsevier Inc. All rights reserved. First edition 1987 Second edition 1991 Third edition 1995 Fourth edition 1999 Fifth edition 2003 Sixth edition 2007 The right of H P Rang, M M Dale, J M Ritter, R J Flower and G Henderson to be identified as authors of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act 1988. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. 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Main Edition ISBN-13 978-0-70203471-8 International Edition ISBN-13 978-1-4377-1933-8 British Library Cataloguing in Publication Data Rang & Dale’s pharmacology. – 7th ed. 1. Pharmacology. I. Pharmacology II. Rang, H. P. III. Dale, M. Maureen. 615.1-dc22 A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1