T HE A DRENERGIC R ECEPTORS

T ^HE A ^DRENERGIC R ^ECEPTORS

T ^{H E} R E C E P T O R S

K ^IM A. N ^EVE , S ^ERIES E ^DITOR

The Adrenergic Receptors: In the 21st Century,

Dianne M. Perez, 2005

The Melanocortin Receptors,

Roger D. Cone, 2000 The GABA Receptors, Second Edition,

S. J. Enna

and Norman G. Bowery, 1997

The Ionotropic Glutamate Receptors,

Daniel T.

Monaghan and Robert Wenthold, 1997

The Dopamine Receptors,

Kim A. Neve and Rachael L. Neve, 1997

The Metabotropic Glutamate Receptors,

P. Jeffrey Conn and Jitendra Patel, 1994

The Tachykinin Receptors,

Stephen H. Buck, 1994 The Beta-Adrenergic Receptors,

EDITED BY

John P. Perkins, 1991

Adenosine and Adenosine Receptors,

Michael Williams, 1990

The Muscarinic Receptors,

Joan Heller Brown, 1989 The Serotonin Receptors,

Elaine Sanders-Bush, 1988 The Alpha-2 Adrenergic Receptors,

Lee Limbird,

1988

The Opiate Receptors,

Gavril W. Pasternak, 1988 The Alpha-1 Adrenergic Receptors,

Robert R.

Ruffolo, Jr., 1987

The GABA Receptors,

S. J. Enna, 1983

The Adrenergic Receptors

In the 21 ^ST Century

Edited by

Dianne M. Perez

Department of Molecular Cardiology The Lerner Research Institute,

The Cleveland Clinic Foundation, Cleveland, OH

© 2006 Humana Press Inc.

999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved.

No part of this book 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. All articles, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher.

Cover design by Patricia F. Cleary

Cover illustration: Fluorescent ligand (QAPB, also known as BODIPY FL-prazosin, 30 nM) binding to α¹-adrenoceptors in isolated smooth muscle cells. The data is displayed as an iso- surface model in which the cell membrane is rendered with a transparent “blue” surface.

Intracellular fluorescent regions, indicating ligand-receptor binding, are colored orange and green in the two cells. Bright “clusters” of fluorescence are shown as red in both cells. Alternative views and explanations of the data are given in Chapter 6 by McGrath and Daly.

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Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 eISBN 1-59259-931-1

Library of Congress Cataloging-in-Publication Data

The adrenergic receptors : in the 21st century / edited by Dianne M. Perez.

p. cm. -- (The receptors)

Includes bibliographical references and index.

ISBN 1-58829-423-4 (alk. paper)

1. Adrenaline--Receptors. 2. Pharmacogenetics. I. Perez, Dianne M. II.Series.

QP364.7.A375 2005 612.4'5--dc22

2005008529

Preface

Our understanding of adrenergic function has advanced considerably in the 15 years since three adrenergic receptor books were published in The Receptors series. In the late 1980s, many of the adrenergic subtypes had not yet been cloned.

Most of the studies during that time focused on traditional pharmacological approaches in selected tissues and cell lines. We learned about structure–function relationships through the manipulation of the drug, not the receptor. We understood that there were multiple subtypes within each class of adrenergic receptors, but the functions of the subtypes were unclear because they seemed to control the same signal transduction and biological processes. Molecular cloning of the receptors led to the realization that there were many different subtypes, some not previously described by the tissue pharmacology. With the genes of these receptors in hand, the field has now advanced with more precise experiments and questions, but it has still suffered from the lack of highly selective ligands and antibodies. Foreseeing that these limitations would not be overcome any time in the near future, scientists in the adrenergic receptor field—using modern genetic approaches—started to redirect their work to answer questions about structure and function and the possible physiological and patho- physiological pathways that would be regulated by adrenergic receptors. The Adrenergic Receptors: In the 21st Century focuses on these modern approaches and was written by the scientists who developed them to elucidate adrenergic receptor function.

Dianne M. Perez

v

Contents

vii

Preface ... v Contributors ... ix Color Plates ... xi

P

I: H

P

1 Adrenergic Receptors: Historical Perspectives From the 20th Century

David B. Bylund ... 3 P

II: S

–F

2 Ligand Binding, Activation, and Agonist Trafficking Angela M. Finch, Valerie Sarramegna,

and Robert M. Graham ... 25 3 New Signal Transduction Paradigms

Kenneth P. Minneman ... 87 4 Regulation of the Cellular Localization and Trafficking

of the Adrenergic Receptors

Michael T. Piascik, Mary Lolis García-Cazarin,

and Steven R. Post ... 107 5 Adrenergic Receptors in Clinical Medicine

Martin C. Michel and Paul A. Insel ... 129 P

III: I

A

R

T

F

6 Use of Fluorescent Ligands and Receptors to Visualize Adrenergic Receptors

John C. McGrath and Craig J. Daly ... 151 7 Localization of Adrenergic Receptor Subtypes and

Transgenic Expression of Fluorescent-Tagged Receptors

Dianne M. Perez ... 173

P

IV: G

A

M

M

8 The α

-Adrenergic Receptors:

Lessons From Knockouts

Paul C. Simpson ... 207 9 The α

-Adrenergic Receptors:

Lessons From Knockouts

Christopher M. Tan and Lee E. Limbird ... 241 10 The β-Adrenergic Receptors:

Lessons From Knockouts

Yang Xiang and Brian Kobilka ... 267 11 Lessons From Overexpressed Mouse Models

Cinzia Perrino, Liza Barki-Harrington,

and Howard A. Rockman ... 293 12 Adrenergic Receptor Signaling Components

in Gene Therapy

Andrea D. Eckhart and Walter J. Koch ... 321 P

V: P

13 Genetic, Molecular, and Clinical Characterization of Adrenergic Receptor Polymorphisms

Stephen B. Liggett ... 339 14 Microarray Analysis of Novel Adrenergic

Receptor Functions

Boyd Rorabaugh, June Yun, and Dianne M. Perez ... 365 P

VI: S

F

E

15 Summary and Future Endeavors

Dianne M. Perez ... 395 Index ... 397

viii Contents

Contributors

ix

L

B

-H

• Division of Cardiology, Duke University Medical Center, Durham, NC

D

B. B

• Department of Pharmacology, University of Nebraska Medical Center, University of Nebraska, Omaha, NE

C

J. D

• Autonomic Physiology Unit, Institute of Biomedical and Life Sciences, Division of Neuroscience and Biomedical Systems,

University of Glasgow, Glasgow, Scotland, UK

A

D. E

• Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA

A

M. F

• Molecular Cardiology Program, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia

M

L

G

-C

• Department of Molecular and Biomedical Pharmacology, The University of Kentucky College of Medicine, Lexington, KY

R

M. G

• Molecular Cardiology Program, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia

P

A. I

• Department of Pharmacology and Medicine, University of California San Diego, San Diego, CA

B

K

• Department of Molecular and Cellular Physiology, Stanford Medical Center, Stanford University, Palo Alto, CA

W

J. K

• Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA

S

B. L

• Cardiopulmonary Research Center, University of Cincinnati College of Medicine, Cincinnati, OH

L

E. L

• Department of Pharmacology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN

J

C. M

G

• Autonomic Physiology Unit, Institute of Biomedical and Life Sciences, Division of Neuroscience and Biomedical Systems, University of Glasgow, Glasgow, Scotland, UK

M

C. M

• Department of Pharmacology, University of Amsterdam, Amsterdam, The Netherlands

K

P. M

• Department of Pharmacology, Emory University,

Atlanta, GA

x Contributors

D

M. P

• Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH C

P

• Division of Cardiology, Duke University Medical Center,

Durham, NC

M

T. P

• Department of Molecular and Biomedical Pharmacology, The University of Kentucky College of Medicine, Lexington, KY

S

R. P

• The Department of Molecular and Biomedical Pharmacology, The University of Kentucky College of Medicine, Lexington, KY

H

A. R

• Division of Cardiology, Duke University Medical Center, Durham, NC

B

R

• Department of Pharmacology, College of Pharmacy, Ohio Northern University, Ada, OH

V

S

• Molecular Cardiology Program, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia P

C. S

• Cardiology Division, San Francisco VA Medical Center,

and the CVRI and Department of Medicine, University of California, San Francisco, CA

C

M. T

• Department of Pharmacology, Merck Research Laboratories, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada

Y

X

• Department of Molecular and Cellular Physiology, Stanford Medical Center, Stanford University, Palo Alto, CA

J

Y

• The Department of Physiology and Pharmacology, Northeastern

Ohio Universities College of Medicine, Rootstown, OH

Color Plates

Color Plates follow p. 148.

Color Plate 1. Confocal imaging of human aortic smooth muscle cells trans- fected with an adenovirus (Fig. 1, Chapter 4; see full caption and discussion on pp. 117–118).

Color Plate 2. Classical AR signaling (Fig. 1, Chapter 11; see full caption and discussion on p. 294).

Color Plate 3. Major mechanisms involved in β-AR desensitization and intern- alization (Fig. 2, Chapter 11; see full caption on p. 296 and discussion on p. 295).

Color Plate 4. Histopathological characteristics of left ventricular specimens taken from mice overexpressing the human β

-AR (Fig. 5, Chapter 11; see full caption on p. 307 and discussion on pp. 306–308).

Color Plate 5. Phylogenetics of β

-AR haplotypes (Fig. 2, Chapter 13; see full caption on p. 342 and discussion on pp. 340–341).

xi