Excitatory Amino Acids: From Genes to Therapy

217 Pages·1998·4.61 MB·English

by  P. H. Seeburg

Ernst Schering Research Foundation Workshop 23
Excitatory Amino Acids
Springer-Verlag Berlin Heidelberg GmbH
Ernst Schering Research Foundation
Workshop 23
Excitatory Amino Acids
From Genes to Therapy
P. H. Seeburg, I. Bresink, L. Turski
Editors
With 45 Figures in 125 Separate Illustrations
Springer
Series Editors: G. Stock and D.-F. Habenicht
ISSN 0947-6075
ISBN 978-3-662-03598-6 ISBN 978-3-662-03596-2 (eBook)
DOI 10.1007/978-3-662-03596-2
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ISSN 0947-6075
23. Excitatory amino acids: from genes to therapy. -1998
Excitatory amino acids: from genes to therapy / P.H. Seeburg ... ed. -Berlin; Heidelberg;
New York; Barcelona; Budapest; Hong Kong; London; Milan; Paris; Santa Clara; Singa-
pore; Tokyo: Springer. 1998
(Ernst Schering Research Foundation Workshop; 23)
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Preface
Glutamate Antagonists: Quo Vade?
Since the beginning of the 1990s, glutamate antagonists have repeat-
edly excited the scientific community through discoveries of their in-
triguing role in physiology and pathology. Until today they have re-
mained the major hope for the therapy of neurodegenerative disorders
in humans. NMDA antagonists have been designed for the treatment of
acute-onset neurodegeneration such as stroke and trauma, and have re-
cently reached the clinics. Unfortunately, the anticipated success of
NMDA antagonists in patients has been limited due to unacceptable
side effects.
In the meantime, AMP A antagonists have left the realm of drug re-
search and are rapidly moving towards the clinic. The expectations and
medical needs, which have changed little over time, are placing devel-
opment of AMPA antagonists under public attention. The enthusiasm
which surrounds AMPA antagonists is great, since they appear to be
safer and to have fewer side effects than the NMDA antagonists.
Research on glutamate receptors has entered the phase of discover-
ing molecular details of the channels and genetic principles, which de-
termine phenotypic characteristics and sensitivity of neurons to the
deleterious influences of nature.
The engineering of transgenic mice with modified expression of
single-receptor subunits has enabled insights into the function, dys-
function, and possible pathology causally related to glutamate recep-
tors.
VI Preface
The participants of the workshop
The meeting on "Excitatory Amino Acids: From Genes to Therapy"
addresses today's emerging questions and discusses new avenues
which glutamate research may take in the future. The entry of AMPA
antagonists into the clinic for first evaluations in humans dominates the
field of today's glutamate research. The picture of kainate receptors is
slowly emerging and coming into focus. These enigmatic receptors
may dominate the field soon, leading to new excitements and novel re-
search efforts.
P. H. Seeburg
l. Bresink
L. Turski
Table of Contents
Glutamate Receptor Channels, RNA Editing, and Epilepsy
P.H. Seeburg, R. Brusa, M. Higuchi, and R. Sprengel
2 Regulation of Glutamate Receptor Gene Expression
in Global Ischemia
D.E. Pellegrini-Giampietro . . . . . . . . . . . . . 19
3 Factors Regulating Excitotoxic Neurodegeneration:
The Role of Calcium and the Mitochondria
R.I. Miller, V.P. Bindokas, D.F. Babcock, J.-P. Lee,
and J.B. Jordan . . . . . . . . . . . . . . . . . . 43
4 Excitotoxicity, Genetics, and Neurodegeneration
in Amyotrophic Lateral Sclerosis
P.l. Shaw .......... . . . . . . . . . . . . . . . .. 65
5 NO-NMDA Receptor Interactions:
A Neuromolecular Approach to Novel Therapeutics
S.A. Lipton, Y.-B. Choi, N.J. Sucher, and H.S.-V. Chen 95
6 Glutamate in Neurodegenerative Disorders:
Phenotype Resulting from Decreased Expression
of AMPA Receptor GluR-B Subunit mRNA in Rats
G. Miiller, U. Endermann, I. Bresink, and L. Turski . . . . . 109
VIII Table of Contents
7 Quantitative Estimation of NMDA Receptor-Mediated
Ca2+ Entry in Central Neurons
O. Caraschuk, T. Plant, and A. Konnerth .......... 127
8 Calcium Permeability of Glutamate-Gated Channels
cl+ -
in the CNS: Functional Role of the Permeable
AMPA Receptor Channels
N. Burnashev ......................... 149
9 Localisation and Surface Expression of the AMPA Receptor
Subunit GluRI Using Green Fluorescent Protein
and Anti-Peptide Antibodies
A. Doherty, A. Irving, C.L. Colling ridge, and 1.M. Henley 161
10 Input-and Output-Specific Segregation
of Amino Acid Neurotransmitter Receptors
on the Surface of Central Neurones
Z. Nusser and R. Shigemoto 187
Subject Index ......................................... 207
Previous Volumes Published in this Series .................. 209
List of Editors and Contributors
Editors
P.H. Seeburg
Max Planck Institute for Medical Research, Department of Molecular Neuro-
science, Jahnstr. 29, 69120 Heidelberg, Germany
I. Bresink
Research Laboratories of Schering AG, Miillerstr. 178, l3342 Berlin,
Germany
L. Turski
Eisai London Research Laboratories, Bernard Katz Building, University Col-
lege London, Gower Street, London WC1E 6BT, UK
Contributors
D.F. Babcock
Department of Pharmacological and Physiological Sciences, The University
of Chicago, 947 East 58th Street (MC 0926), Chicago, IL 60637, USA
I. Bresink
Research Laboratories of Schering AG, Miillerstr. 178, 13342 Berlin,
Germany
V.P. Bindokas
Department of Pharmacological and Physiological Sciences, The University
of Chicago, 947 East 58th Street (MC 0926), Chicago, IL 60637, USA
x List of Editors and Contributors
R. Brusa
Schering Plough Research Institute, Via Olgettina 58, 20132 Milan, Italy
N. Burnashev
Max-Planck-Institute of Medical Research, Department of Cell Physiology,
Jahnstr. 29,69120 Heidelberg, Germany
H.S.-V. Chen
CNS Research Institute, Brigham and Women's Hospital and Harvard Medi-
cal School, 221 Longwood Avenue-LMRC, Boston, MA 02115, USA
Y.-B. Choi
CNS Research Institute, Brigham and Women's Hospital and Harvard Medi-
cal School, 221 Longwood Avenue-LMRC, Boston, MA 02115, USA
G.L. Colling ridge
Department of Anatomy, Medical School, University of Bristol, Bristol,
BS8 lTD, UK
A. Doherty
Department of Anatomy, Medical School, University of Bristol, Bristol,
BS8ITD, UK
U. Endermann
Research Laboratories of Schering AG, Miillerstr. 178, 13342 Berlin,
Germany
o. Garaschuk
Institute of Physiology I, University of Saarland, 66421 Homburg, Germany
1.M. Henley
Department of Anatomy, Medical School, University of Bristol, Bristol,
BS8 lTD, UK
M. Higuchi
Max Planck Institute for Medical Research, Department of Molecular Neuro-
science, Jahnstr. 29, 69120 Heidelberg, Germany
A. Irving
Department of Biomedical Sciences, Institute of Medical Sciences, Forrester
Hill, University of Aberdeen, Aberdeen, AB25 2ZD, UK