The Serotonin Receptors: From Molecular Pharmacology to Human Therapeutics

628 Pages·2006·7.846 MB·English

by  Wesley K. Kroeze, Bryan L. Roth (auth.), Bryan L. Roth MD, PhD (eds.)

T S R
HE EROTONIN ECEPTORS
T R
H E E C E P T O R S
K A. N , S E
IM EVE ERIES DITOR
The Serotonin Receptors: From Molecular Pharmacology
to Human Therapeutics, EDITED BY Bryan L. Roth, 2006
The Adrenergic Receptors: In the 21st Century, EDITED BY
Dianne M. Perez, 2005
The Melanocortin Receptors, EDITED BY Roger D. Cone, 2000
The GABA Receptors, Second Edition, EDITED BY S. J. Enna
and Norman G. Bowery, 1997
The Ionotropic Glutamate Receptors, EDITED BY Daniel T.
Monaghan and Robert Wenthold, 1997
The Dopamine Receptors, EDITED BY Kim A. Neve and Rachael
L. Neve, 1997
The Metabotropic Glutamate Receptors, EDITED BY P. Jeffrey
Conn and Jitendra Patel, 1994
The Tachykinin Receptors, EDITED BY Stephen H. Buck, 1994
The Beta-Adrenergic Receptors, EDITEDBY John P. Perkins, 1991
Adenosine and Adenosine Receptors, EDITED BY Michael
Williams, 1990
The Muscarinic Receptors, EDITED BY Joan Heller Brown, 1989
The Serotonin Receptors, EDITED BY Elaine Sanders-Bush, 1988
The Alpha-2 Adrenergic Receptors,EDITEDBY Lee Limbird, 1988
The Opiate Receptors, EDITED BY Gavril W. Pasternak, 1988
The Alpha-1 Adrenergic Receptors,EDITED
BY Robert R. Ruffolo, Jr., 1987
The GABA Receptors, EDITED BY S. J. Enna, 1983
The Serotonin
Receptors
From Molecular Pharmacology
to Human Therapeutics
Edited by
Bryan L. Roth, MD, PhD
Department of Biochemistry
Case Western Reserve University–School of Medicine
Cleveland, OH
© 2006 Humana Press Inc.
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Cover design by Patricia F. Cleary
Cover illustration: Figure 3 from Chapter 9, “Cellular and Subcellular Localization of Serotonin
Receptors in the Central Nervous System,” by L. Descarries, V. Cornea-Hébert, and M. Riad
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Library of Congress Cataloging-in-Publication Data
The serotonin receptors : from molecular pharmacology to human therapeutics / edited by
Bryan L. Roth.
p. cm. — (The receptors)
Includes bibliographical references and index.
ISBN 1-58829-568-0 (alk. paper)
1. Serotonin—Receptors. 2. Serotonin—Physiological effect. 3. Serotoninergic mecha
nisms. I. Roth, Bryan L. II. Series.
QP801.S4.S474 2006
612.8’042—dc22 2005029055
Preface
It has been nearly 20 years since the last Humana Press book devoted to
serotonin (5-hydroxytryptamine; 5-HT) receptors has appeared. Since then, the
field of 5-HT receptors has undergone a revolution due to the discovery of many
additional 5-HT receptors. Although 5-HT was chemically elucidated in 1948 by
Page and colleagues (Rapport et al., 1948) and 5-HT receptors initially classified
in 1957 (Gaddum and Picarelli, 1957), the complexity of 5-HT pharmacology
was not fully appreciated until the late 1970s and early 1980s when many puta-
tive 5-HT receptors were identified by radioligand binding studies (e.g., 5-HT1A,
5-HT2, 5-HT1E and so on) (Leysen et al., 1979; Hamon et al., 1980; Peroutka
et al., 1981; Leonhardt et al., 1989). The first 5-HT receptors were cloned in 1988
(Fargin et al., 1988; Julius et al., 1988) and the discovery of 14 distinct human
5-HT receptors since then ushered in the era of 5-HT receptor molecular biology
(Kroeze et al., 2003). The cloning and sequencing of 5-HT receptors has also
revealed the presence of post-transcriptionally modified mRNA species (RNA
editing) (Burns et al., 1997) as well as naturally occurring mutations and their
relations to various diseases (e.g., single nucleotide polymorphisms; SNPs)
(Arranz et al., 1995).
The identification of the amino acid sequences of 5-HT receptors has allowed
us to predict how 5-HT and related agonists bind to and activate 5-HT receptors
(Shapiro et al., 2000; Shapiro et al., 2002). The hope has been that this informa-
tion will lead, eventually, to the development of novel, subtype-selective 5-HT
receptor agonists and antagonists (Kroeze et al., 2002).
The first several chapters of The Serotonin Receptors: From Molecular Phar-
macologyto Human Therapeutics are aimed at reviewing our knowledge of the
molecular and structural biology of 5-HT receptors, followed by our current under-
standing of 5-HT receptor pharmacology. The elucidation of the sequences of 5-
HT receptors has also facilitated the development of highly selective tools for
mapping the distribution of 5-HT receptors. These tools include selective 5-HT
receptor antibodies and hybridization probes. The use of these biochemical probes
has revealed an unexpected complexity in both the cellular and subcellular distri-
bution of 5-HT receptors.
The next few chapters describe the anatomical, cellular, and subcellular dis-
tribution of 5-HT receptors. Because of the plethora of receptors and receptor
subtypes, however, it has been exceedingly difficult to identify the physiological
role of various 5-HT receptors using pharmacological tools. A powerful approach
v
vi Preface
to elucidating the physiological role of 5-HT receptors was to use mice in which
5-HT receptors were deleted (e.g., knockout mice); the first 5-HT receptor knock-
outs were reported in 1994 (Saudou et al., 1994) and, since then, nearly all 5-HT
receptors have been “knocked-out”—typically with novel phenotypes (Tecott et
al., 1995; Brunner et al., 1999).
The final chapters review our understanding the physiological role(s) of 5-HT
receptors based mainly on studies performed in genetically engineered mice.
This book represents our collective attempts to provide the reader with a “snap-
shot” of the 5-HT receptor field circa 2006. The scope of the book is vast,
proceeding from the genomic to the therapeutic. Because it is unlikely that any
reader will devote the time to reading the entire book cover-to-cover, each chap-
ter has been designed to represent a complete review of the particular field. Thus,
each chapter begins with a short introduction to 5-HT receptors and then pro-
ceeds to review the particular subfield in depth. Not surprisingly, therefore, the
enterprising reader will find some overlap between various introductory sec-
tions.
Acknowledgments
I would like to especially thank Mr. Jon Evans who has tirelessly collected,
edited, and collated the finished chapters and who has done most of the “leg
work” associated with this book. Without Jon’s devotion to this task, the book
would never have been completed. Any omissions and errors are my sole respon-
sibility. I would also like to thank my wife Judith and my daughter Rachel for
their warmth and understanding during the gestation of this book. Lastly, I dedi-
cate this book to “beings throughout the ten directions—hands palm-to-palm.”
Bryan L. Roth, MD,PhD
References
Arranz M, Collier D, Sodhi M, Ball D, Roberts G, Price J, Sham P, and Kerwin R.
Association between clozapine response and allelic variation in 5-HT2A receptor gene.
Lancet 1995;346:281–282.
Brunner D, Buhot MC, Hen R, and Hofer M. Anxiety, motor activation, and maternal-
infant interactions in 5HT1B knockout mice. Behav Neurosci 1999;113:587–601.
Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, and
Emeson RB. Regulation of serotonin-2C receptor G-protein coupling by RNA editing
[see comments]. Nature 1997;387:303–308.
Fargin A, Raymond JR, Regan JW, Cotecchia S, Lefkowitz RJ, and Caron MG. The
genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the
5-HT1A receptor. Nature 1988;335:358–360.
Gaddum JH and Picarelli ZP. Two kinds of tryptamine receptors. Br J Pharmacol
1957;12:323–328.
Preface vii
Hamon M, Nelson DL, Herbet A. and Glowinski J. Multiple receptors for serotonin
in the rat brain. Adv Biochem Psychopharmacol 1980;21:223–233.
Julius D, MacDermott AB, Axel R, and Jessell TM. Molecular characterization of a
functional cDNA encoding the serotonin 1c receptor. Science 1988;241:558–564.
Kroeze WK, Kristiansen K, and Roth BL. Molecular biology of serotonin receptors
structure and function at the molecular level. Curr Top Med Chem 2002;2:507–528.
Kroeze WK, Sheffler DJ, and Roth BL. G-protein-coupled receptors at a glance. J Cell
Sci 2002;116:4867-9.
Leonhardt S, Herrick-Davis K, and Titeler M. Detection of a novel serotonin receptor
subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. J Neurochem
1989;53:465–471.
Leysen JE, Gommeren W, Laduron PM, et al. Distinction between dopaminergic and
serotonergic components of neuroleptic binding sites in limbic brain areas. Biochem
Pharmacol 1979;28:447–448.
Peroutka SJ, Lebovitz RM, and Snyder SH. Two distinct serotonin receptors with
distinct physiological functions. Science 1981;212:827-829.
Rapport MM, Green AA, and Page IH. Crystalline serotonin. Science 1948;108:329.
Saudou F, Amara DA, Dierich A, et al. Enhanced aggressive behavior in mice lacking
5-HT1B receptor. Science 1994;265:1875–1878.
Shapiro DA, Kristiansen K, Kroeze WK, and Roth BL. Differential modes of agonist
binding to 5-hydroxytryptamine(2A) serotonin receptors revealed by mutation and
molecular modeling of conserved residues in transmembrane region 5. Mol Pharmacol
2000;58:877–886.
Shapiro DA, Kristiansen K, Weiner DM, Kroeze WK, and Roth BL. Evidence for a
model of agonist-induced activation of 5-HT2A serotonin receptors which involves the
disruption of a strong ionic interaction between helices 3 and 6. J Biol Chem 2002;18:18.
Tecott LH, Sun LM, Akana SF, et al. Eating disorder and epilepsy in mice lacking 5-
HT2c serotonin receptors [see comments]. Nature 1995;374:542–546.
Contents
Preface...............................................................................................................v
Contributors.....................................................................................................xi
Color Plate....................................................................................................xvii
1 Molecular Biology and Genomic Organization
of G Protein–Coupled Serotonin Receptors
Wesley K. Kroeze and Bryan L. Roth ....................................................1
2 Structure and Function Reveal Insights in the Pharmacology
of 5-HT Receptor Subtypes
Richard B. Westkaemper and Bryan L. Roth.......................................39
3 Polymorphic and Posttranscriptional Modifications of 5-HT
Receptor Structure: Functional and Pathological Implications
Marilyn A. Davies, Chiao-ying Chang, and Bryan L. Roth................59
4 Strategies for the Development of Selective Serotonergic Agents
Richard A. Glennon..............................................................................91
5 5-HT Receptor Signal Transduction Pathways
John R. Raymond, Justin H. Turner, Andrew K. Gelasco,
Henry B. Ayiku, Sonya D. Coaxum, John M. Arthur,
and Maria N. Garnovskaya.........................................................143
6 Agonist-Directed Trafficking of 5-HT Receptor-Mediated Signal
Transduction
Kelly A. Berg and William P. Clarke ................................................207
7 Identification of 5-HT and 5-HT Receptor-Interacting
2 4
Proteins:A Proteomic Approach
Joël Bockaert, Carine Bécamel, Lara Joubert, Sophie Gavarini,
Aline Dumuis, and Philippe Marin .............................................237
ix
x Contents
8 5-HT Receptor-Associated Proteins (FRAPs): Relevance for
Targeting, Trafficking, and Signal Transduction
Zongqi Xia, Douglas J. Sheffler, and Bryan L. Roth ........................257
9 Cellular and Subcellular Localization of Serotonin Receptors
in the Central Nervous System
Laurent Descarries, Virginia Cornea-Hébert,
and Mustapha Riad......................................................................277
10 Chemical Neuroanatomy of 5-HT Receptor Subtypes in the
Mammalian Brain
Guadalupe Mengod, M. Teresa Vilaró, Roser Cortés,
Juan F. López-Giménez, Andreu Raurich,
and José M. Palacios...................................................................319
11 Modulation of the Neuronal Activity and Neurotransmitter
Release by 5-HT and 5-HT Receptors
1A 1B/1D
Pau Celada, Albert Adell, and Francesc Artigas.......................365
12 Electrophysiology of 5-HT Receptors and Relevance for
2A
Hallucinogen and Atypical Antipsychotic Drug Actions
Evelyn K. Lambe and George K. Aghajanian...................................403
13 The Emergence of 5-HT Receptors as Targets to Avoid
2B
in Designing and Refining Pharmaceuticals
Vincent Setola and Bryan L. Roth .....................................................419
14 The 5-HT Receptor
3
Andrew J. Thompson, Li Zhang, and Sarah C. R. Lummis...............439
15 5-HT and 5-HT Receptors as Targets for Drug Discovery
3 4
for Dementia
Frank Lezoualc’h and Magali Berthouze..........................................459
16 Electrophysiological Properties of G(cid:68) -Coupled 5-HT
s
Receptors (5-HT , 5-HT , 5-HT )
4 6 7
Rodrigo Andrade................................................................................481
17 5-HT Receptors as Targets for the Treatment of Cognitive
6
Deficits in Schizophrenia
Rudy Schreiber, Andrew Sleight, and Marie Woolley.......................495