Neuropeptide Y and Related Peptides

555 Pages·2004·10.331 MB·English

by  K. Tatemoto (auth.), Professor Martin C. Michel (eds.)

Handbook of
Experimental Pharmacology
Volume 162
Editor-in-Chief
K.Starke, Freiburg i.Br.
Editorial Board
G.V.R. Born, London
M. Eichelbaum, Stuttgart
D.Ganten, Berlin
F. Hofmann, Miinchen
B.Kobilka, Stanford, CA
w.
Rosenthal, Berlin
G.Rubanyi, Richmond, CA
Springer-Verlag Berlin Heidelberg GmbH
Neuropeptide Y
and Related Peptides
Contributors
M. Alfalah, A. Beck-Sickinger, S. Bedoui, A. Brennauer,
A. Buschauer, e. Carvajal, H.M. Cox, W.R. Crowley,
O.Della-Zuana, S.Dove, Y. Dumont, J.-1. Fauchere,
M. Feletou, J.P.Galizzi, M. Heilig, H. Herzog, S.von Horsten,
T. Hoffmann, N.P. Hyland, S.P. Kalra, P.S. Kalra, T. Karl,
A. Kask, M. Lonchampt, N.R. Levens, M.e. Michel, K. Morl,
R. Pabst, J.P.Redrobe, R. Quirion, K. Tatemoto, T.E. Thiele,
CiD. Wrann
Editor
Martin C. Michel
, Springer
Professor
Martin C. Michel
Academisch Medisch Centrum
Afd. Farmacologie & Farmacotherapie
Meibergdreef 15, 1105 AZ Amsterdam
The Netherlands
e-mail: [email protected]
With 81 Figures and 23 Tables
ISSN 0171-2004
ISBN 978-3-642-62282-3
Library of Congress Cataloging-in-Publication Data
Neuropeptide Yand related peptides / contributors M. Alfalah ... [et al.) ; editor Martin C. Michel. p.
cm. - (Handbook of experimental pharmacology ; v. 162)
Includes bibliographical references and index
ISBN 978-3-642-62282-3 ISBN 978-3-642-18764-3 (eBook)
DOI 10.1007/978-3-642-18764-3
1. Neuropeptide Y- Physiological effect. 2. Neuropeptide Y- Derivatives-Physiological effect. 1. Alfa
lah, M. (Marwan) II. Michel, Martin C., 1959-III. Series. QP905.H3 voI. 162
[QP552.N38) 615'.5. s-dc22 [573.8'48) 20030556335'.5
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Preface
Alittle more than 20years have now passedsincethe original discoveryofneuro
peptide Y(NPY)by Tatemoto and colleagues.Meanwhilea Medlinesearch for the
keyword 'NPY' yields more than 7,000hits, with a steady400-500 per year in the
last decade.
500
...
400
C1I
CII
.>...
300
CII
Q.
...
III
200
CII
Q.
C1I
Q. 100
0
1980 1985 1990 1995 2000 2005
year
Fig.1 Numberofpapersretrieved byyearofpublicationfrom Medlineunderthekeyword'NPV'
Papers devoted exclusively to the closely related peptide YYand pancreatic po
lypeptide are not even included in this statistic.Thus,it is not surprising that the
field ofNPYresearch has made remarkableprogress and is comingofage.
Phylogenetic research has shown that NPY is an evolutionary very old and
highlyconserved peptide. Members ofthe NPYfamily ofpeptides act on specific
G-protein coupled receptors, ofwhich fivesubtypes have been cloned in avariety
ofspecies and whose signaltransduction is beingunraveled. Cloning of the genes
for NPYand its receptors has enabled the generation of transgenic and knockout
animals. Using such tools we now understand major aspects ofthe physiological
role of NPY not only in the brain but also, for example, in the peripheral tissues
ofthe cardiovascular, gastrointestinal and immune system. While NPYlargelyex
erts these effects as a neurotransmitter, the related peptide YYand pancreatic po
lypeptide predominantly act as hormones. Numerous peptide analogs and non-
VI Preface
peptide ligands acting on NPYreceptors, often in a subtype-selective manner,
havebeen described.Theyset the stagefor the finalact,the definition ofthe role
of NPY in human health and disease and ultimately the manipulation of this sy
stemintreatingpatients.
The present volume addresses allofthe above topics byestablished leaders in
their respective areas. Iwould liketo take this opportunity to thank allcontribu
tors for the time and effort they have spent in preparing their chapters and also
Mrs. Susanne Dathe of Springer-Verlagwho expertly supported the project. On
behalf of all contributors Ihope that experienced NPYaficionados willfind new
and usefuladditional information in this volume and that newcomers to the field
willdiscoverhowmuch excitingresearch this stillhasto offer.
August2003 Martin C.Michel,Amsterdam
List ofContributors
(Theiraddressescanbefoundatthebeginningoftheirrespectivechapters.)
Alfalah, M. 23 Kalra, S.P. 221
Kalra, P.S. 221
Beck-Sickinger, A.G. 479 Karl,T. 23
Bedoui, S. 23,409 Kask, A. 101
Brennauer, A. 505
Buschauer,A. 505 Larhammar, D. 75
Larson, E.T. 75
Carvajal, e. 101 Levens,N.R. 283
Cox, H.M. 45,389 Lonchampt,M. 283
Crowley, W.R. 185
Michel,M.e. 45,361
Della-Zuana, O. 283 Morl, K. 479
Dove,S. 505 Morris,M.J. 327
Dumont, Y. 101
Pabst, R. 23,409
Fauchere,J.-L. 283
Peletou,M. 283 Quirion,R. 101
Fredriksson, R. 75
Redrobe,J.P. 101
Galizzi, J.-P. 283
Salaneck, E. 75
Heilig, M. 251
Herzog, H. 447 Tatemoto, K. 1
Horsten, S.von 23,409 Thiele, T.E. 251
Hoffmann,T. 23
Holliday,N.D. 45 Westfall, T.e. 137
Hyland, N.P. 389 Wrann, e.D. 23
List ofContents
Neuropeptide Y: Historyand Overview .
K. Tatemoto
PP,PYYand NPY:Synthesis, Storage, Releaseand Degradation. ......... 23
S.vonHtirsten, T. Hoffmann,M.Alfalah,C.D. Wrann, T. Karl,
R.Pabst, S.Bedoui
NPYReceptor Subtypes and TheirSignal Transduction. ............... 45
N.D.Holliday, M.C.Michel,H.M.Cox
Phylogeny ofNPY-FamilyPeptides and Their Receptors. .............. 75
D.Larhammar,R.Fredriksson, E.T. Larson, E.Salaneck
Neuropeptide Yand Its ReceptorSubtypes in the Central Nervous System:
Emphasis on TheirRolein Animal Models ofPsychiatricDisorders. ..... 101
].P. Redrobe, C.Carvajal,A.Kask, Y. Dumont,R.Quirion
PrejunctionalEffectsofNeuropeptide Yand Its Roleas aCotransmitter. .. 137
T.C. Westfall
Neuroendocrine Actions OfNeuropeptide Y......................... 185
WR. Crowley
NPY: ANovelOnlOffSwitch for Control ofAppetite and Reproduction. .. 221
S.P. Kalra, P.S. Kalra
Behavioral EffectsofNeuropeptide Y. .............................. 251
T.E.Thiele,M. Heilig
X ListofContents
NPYEffectson Food Intake and Metabolism......................... 283
N.R. Levens, M.Feletou,I.-P. Galizzi, I.-I.Fauchere,O.Della-Zuana,
M.Lonchampt
Neuropeptide YandCardiovascularFunction ........................ 327
M,J.Morris
Neuropeptide Yand the Kidney.................................... 361
M.e. Michel
NPY-Like Peptides, YReceptors and Gastrointestinal Function. ......... 389
N.P. Hyland,H.M.Cox
NPYand ImmuneFunctions: Implications for Health and Disease ....... 409
S.Bedoui, R.Pabst,S.von Horsten
Transgenic and KnockoutModels in NPYResearch ................... 447
H. Herzog
Structure-Activity Relationship
ofPeptide-Derived Ligandsat NPYReceptors. ....................... 479
K.Morl,A.G.Beck-Sickinger
Structure-ActivityRelationships
ofNonpeptide Neuropeptide YReceptor Antagonists. ................. 505
A.Brennauer, S.Dove,A.Buschauer
Subject Index.................................................. 547
Neuropeptide Y: History and Overview
K.Tatemoto
DepartmentofMolecularPhysiology,InstituteforMolecularandCellularRegulation,
Gunma University,371-8512 Maebashi,Japan
e-mail:[email protected]
Introduction . . . . . . . . . . . . . . . . . 2
2 IsolationandPrimaryStructuresofNPY. 2
2.1 DiscoveryofNPY . . . . . 2
2.2 PrimaryStructureofNPY. . . 3
2.3 NPYmRNA. . . . . . . . . . . 4
3 CellularLocalizationofNPY. 4
3.1 NPYinthe Peripheral Nervous System. 4
3.2 NPYinthe Central Nervous System . . 5
4 Studieson the Receptorsand PhysiologicalFunctionsofNPY(1982-1992). 5
4.1 PeripheralActions ofNPY . 5
4.1.1Cardiovascular Response . . 5
4.1.2 HormoneSecretion . . . . . 6
4.2 CentralActions ofNPY . . . 6
4.2.1 Cardiovascular Response . . 6
4.2.2CircadianRhythms . . . . . 6
4.2.3 Food Intakeand Energy Expenditure 6
4.2.4 HormoneSecretion and Reproduction. 7
4.2.5Stress,Depression,Anxiety,and Pain . 7
4.2.6Seizures. . . . . . . . . . . . . . . . . . 8
4.3 NPYReceptor Bindingand IntracellularSignaling. 8
4.4 NPYReceptor Agonistsand Antagonists. . . . . . . 8
4.5 NPYReceptor Subtypes. . . . . . . . . . . . . . . . 8
5 Studieson the ReceptorsandPhysiologicalFunctionsofNPY(1992-2002). 9
5.1 Cloning ofNPYReceptor Subtypes. 9
5.1.1Y1Receptor. . . . . . 10
5.1.2Y2Receptor. . . . . . 10
5.1.3PutativeY3Receptor. 10
5.1.4Y Receptor. 10
4
5.1.5 Y5Receptor. . . . . . 11
5.1.6Y6Receptor . . . . . . 11
5.2 SelectiveNPYReceptor Agonistsand Antagonists . 11
5.3 NPYReceptor Subtypesand TheirPhysiological Functions . 12
5.3.1CardiovascularResponse. . . . . . . 12
5.3.2Circadian Rhythms . . . . . . . . . . 12
5.3.3Food Intake and EnergyExpenditure 12