Insights into Receptor Function and New Drug Development Targets

211 Pages·2006·7.076 MB·English

by  Lutz Birnbaumer, Eda Yildirim, Yanhong Liao (auth.), Michael Conn Ph.D., Claude Kordon Ph.D., Yves Christen Ph.D. (eds.)

researchandperspectivesinendocrineinteractions
M. Conn C. Kordon
Y. Christen (Eds.)
Insights into
Receptor Function
and New Drug
Development Targets
With58Figuresand14Tables
123
Conn,Michael,Ph.D.
DivisionsofNeuroscienceandReproductiveBiology
DepartmentsofPhysiologyandPharmacology
andCellandDevelopmentalBiology
505NW185thAvenue
OregonNationalPrimateResearchCenter
OregonHealthandScienceUniversity
Beaverton,Oregon97006
USA
email:[email protected]
Kordon,Claude,Ph.D. Christen,Yves,Ph.D.
InstitutNecker FondationIPSEN
156,ruedeVaugirard PourlaRechercheThérapeutique
75015Paris 24,rueErlanger
France 75781ParisCedex16
e-mail:[email protected] France
e-mail:[email protected]
ISBN-10 3-540-34446-2 SpringerBerlinHeidelbergNewYork
ISBN-13 978-3-540-34446-9 SpringerBerlinHeidelbergNewYork
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Introduction
“Youcannotsupposethatatomsofthesameshapeareentering
ournostrilswhenstinkingcorpsesareroastingaswhenthestage
isfreshlysprinkled withsaffronofCilicia andanear-by alter
exhales the perfumes of the Orient. You cannot attribute the
same compositionto sightsthatfeast the eye with colourand
tothosethatmakeitsmartandweeporthatappearloathsome
andrepulsivethroughsheerugliness.Nothingthatgratifiesthe
sense is ever without a certain smoothness of the constituent
atoms. Whatever, on the other hand, is painful and harsh is
characterizedbyacertainroughnessofmatter”
(Lucretius,NatureoftheUniverse,BookII).
The origin of the concept of the ligand-receptor interaction clearly stretches back
to the times of our philosophical forbearers, but it is only in the recent part of the
currentcenturythatwehaveaggressivelyharnessedthepowerofourunderstanding
ofstructure-activityrelationshipsinordertoguidetheprocessofdrugdesign.Still
morerecentlycametheapproachofchemicalalterationofdrugchemistryinorderto
modifytheirpharmacologicalproperties.
Wearenowonthevergeofviewingeffectormoleculesandotherregulatorysitesas
therapeutictargetsfortheameliorationofhumanandanimaldisease.Therecognition,
for example, that mutant proteins are frequently misrouted molecules, rather than
functionallydefectiveones,changesourapproachto“inbornerrorsofmetabolism”and
offersnewapproachesforpharmacologicaldiscovery,basedonrescueofreceptors,ion
channelsandenzymeswithpharmacoperones.Ionchannels,regulatorsofG-protein
signaling and enzymes engaged in regulation, now present opportunities for drug
development.
The state of our art also benefits by the availability of superior tools that allow
measurementofinteractionsandaffordunprecedentedinsightintothebiomolecular
interactionsthatpresentnovelapproachestodrugdesign.
Itwasinthisspiritofexcitementthatthiscolloquiumwasorganizedduringearly
2004,atdiscussionsheldinSanDiegoandLisbon.Theresultoftheseplansbrought
togetherleaders,frommanycountriesandacademicdisciplines,toaddressnovelsites
of pharmacologic intervention with a common view of improving drug design by
diversifyingtheapproach,duringtheColloqueMédecineetRechercheheldinParis
onDecember5,2005.
VI Introduction
Theorganizersofthismeetingwouldliketothankthepresentersandauthorsofthe
articlesinthisvolume,alongwiththeexpertstaffatFondationIPSEN,fortheirtimely
submissionandtheprocessingofarticlesrespectively,whichenabledproductionof
acurrentvolume.Wehopethatreaders whounabletoattendthemeetingwilltake
someoftheexcitementofthescientificinteractionfromthisvolume.
Paris,December2005 ClaudeKordon
YvesChristen
MichaelConn
TableofContents
MolecularandfunctionaldiversityoftheTRPCfamilyofionchannels.
TRPCchannelsandtheirroleinROCE/SOCE
L.Birnbaumer,E.Yildirim,Y.Liao,J.Abramowitz ........................... 1
FunctionalRescueofMisfoldedReceptorMutants
S.P.Brothers,P.M.Conn .................................................. 23
Obesity-relatedmutationsofleptinandmelanocortinreceptors
C.Lubrano,B.Dubern,K.Clément ......................................... 35
cAMP-andcGMP-dependentcontroloflipolysisandlipidmobilization
inhumans:putativetargetsforfatcellmanagement
M.Lafontan,M.Berland,C.Sengenes,C.Morod,F.Crampes,J.Galitzky......... 53
Central Neuropeptide Receptors Involved in Water Balance:
ApplicationtoApelin
X.Iturrioz,A.Reaux-LeGoazigo,A.Hus-Citharel,N.DeMota,L.Bodineau,
A.Frugière,S.ElMessari,N.Chartrel,C.Kordon,A.Beaudet,H.Vaudry,F.Moos,
C.Llorens-Cortes ........................................................ 79
Targeting regulators of G protein signaling (RGS proteins)
toenhanceagonistspecificity
R.R.Neubig ............................................................. 93
DimericGPCRs:whatdidwelearnfromthemetabotropicglutamatereceptors?
J.P.Pin,C.Goudet,J.Kniazeff,V.Hlavackova,C.Brock,V.Binet,D.Maurel,
P.Rondard,J.Blahos,L.Prezeau ........................................... 105
Guidingprinciplesappliedinthedesign
ofGPCR-selectivehypothalamichormoneagonistsandantagonists
J.Rivier,J.Gulyas,J.Erchegyi,S.C.Koerber,C.R.R.Grace,R.Riek,M.DiGruccio,
M.Perrin,C.Rivier,V.Eltschinger,B.Waser,R.Cescato,J.C.Reubi,W.andVale .. 117
MutationsinGproteinsandGprotein-coupledreceptors
inhumanendocrinediseases
A.Spiegel ............................................................... 139
Amoleculardissectionoftheglycoproteinhormonereceptors
G.Vassart,L.Pardo,S.Costagliola ......................................... 151
VIII TableofContents
ReceptorTyrosineKinasesasTargetsforCancerTherapyDevelopment
A.Gschwind,O.M.Fischer,A.Ullrich ....................................... 167
Targetsforpituitarytumortherapy
S.Melmed .............................................................. 179
Theendogenouscannabinoidsysteminthecontrol
offoodintakeandenergybalance
A.A.Izzo................................................................ 189
SubjectIndex ........................................................... 201
ListofContributors
Abramowitz,Joel
LaboratoryofSignalTransduction,DivisionofIntramuralResearch,
NationalInstituteofEnvironmentalHealthSciences,NationalInstitutesofHealth,
DepartmentofHealthandHumanServices,111T.W.AlexanderDrive,
ResearchTrianglePark,NorthCarolina27709,USA
Beaudet,Alain
MontréalNeurologicalInstitute,FondsdelaRechercheenSantéQuébec,
500,RueSherboockeOuest,Bureau800,UniversitéMcGill,Montréal,QuebecH3A3C6,
Canada,[email protected]
Berlan,Michel
UnitédeRecherchessurlesObésités,UniversitéPaulSabatier,
InstitutLouisBugnardIFR31,31432Toulouse,France
Blahos,Jaroslav
Dept.ofMolecularPharmacology,InstituteofExperimentalMedicine,
AcademyofScienceofCzechRebublic,Videnska1083,14220Prague4,CzechRepublic
Binet,Virginie
InstituteofFunctionalGenomic,DepartmentofMolecularPharmacology,
CNRSUMR5203,INSERMU661,UniversitédeMontpellier1,
UniversitédeMontpellier2,Montpellier,France
Birnbaumer,Lutz
LaboratoryofSignalTransduction,DivisionofIntramuralResearch,
NationalInstituteofEnvironmentalHealthSciences,NationalInstitutesofHealth,
DepartmentofHealthandHumanServices,111T.W.AlexanderDrive,
ResearchTrianglePark,NorthCarolina27709,USA,[email protected]
Blahos,Jaroslav
Dept.ofMolecularPharmacology,InstituteofExperimentalMedicine,
AcademyofScienceofCzechRebublic,Videnska1083,14220Prague4,CzechRepublic
Bodineau,Laurence
InsermU691,CollègedeFrance,11,PlaceMarcelinBerthelot,75005Paris,France
X ListofContributors
Brock,Carsten
InstituteofFunctionalGenomic,DepartmentofMolecularPharmacology,
CNRSUMR5203,INSERMU661,UniversitédeMontpellier1,
UniversitédeMontpellier2,Montpellier,France
Brothers,ShaunP.
DivisionofNeuroscience,OregonNationalPrimateResearchCenter,
DepartmentofPhysiologyandPharmacology,OregonHealthandScienceUniversity,
505NW185thAvenue,Beaverton,Oregon97006,USA
Cescato,Renzo
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology,
UniversityofBerne,Murtenstrasse31P.O.Box62,3010Berne,Switzerland
Clement,Karine
Inserm“Avenir”,UniversitéPierreetMarieCurie–Paris6,
IFR58,CHRUPitiéSalpétrière–,ServicedeNutrition-Hôtel-Dieu,
PlaceduParvisNotre-Dame,75004Paris,France,[email protected]
Chartrel,Nicolas
Laboratoired’EndocrinologieMoléculaire,InsermU413,UniversitédeRouen,
PlaceÉmileBlondel,76821MontSaintAignanCedex,France
Conn,Michael
DivisionsofNeuroscienceandReproductiveBiology,
DepartmentsofPhysiologyandPharmacologyandCellandDevelopmental,Biology,
505NW185thAvenue,OregonNationalPrimateResearchCenter,
OregonHealthandScienceUniversity,Beaverton,Oregon97006,USA,
[email protected]
Costagliola,Sabine
IRIBHM,UniversitéLibredeBruxelles,CampusErasme,808,RoutedeLennik,
1070Bruxelles,Belgique
Crampes,François
UnitédeRecherchessurlesObésités,UniversitéPaulSabatier,
InstitutLouisBugnardIFR31,31432Toulouse,France
DeMota,Nadia
InsermU691,CollègedeFrance,11,PlaceMarcelinBerthelot,75005Paris,France
DiGruccio,Michael
TheClaytonFoundationLaboratoriesforPeptideBiology,
TheSalkInstituteforBiologicalStudies,10010N.TorreyPinesRoad,LaJolla92037,
USA