多巴胺受体的结构和功能

,,(,,510280)[],,Tourette,,,[];;StructureandfunctionofdopaminereceptorsLIFan,SHUSi2yun,BAOXin2min(InstituteforNeuroscienceofFirstMilitaryMedicalUniversity,ZhujiangHospital,Guangzhou510280,China)[Abstract]Dopamine(DA)isthemostabundantcatecholaminergicneurotransmitterinthebrain.TheinvolvementandimportanceofDAasaneurotransmitterintheregulationofdifferentphysiologicalfunctionsinthecentralnervoussys2tem(CNS)arewellknow.DeregulationofthedopaminergicsystemhasbeenlinkedwithParkinsondisease,Tourettesyndrome,schizophrenia,attentiondeficithyperactivedisorder(ADHD)andgenerationofpituitarytumours.Thisreviewfocusesonthepharmacologicalandbiochemicalfeaturessharedbythedopaminereceptors.Thedistributionofthediffer2entdopaminereceptorsintheCNSandtheirfunctionespeciallyassociatedwithlearningandmemoryareemphasized.[Keywords]dopamine;dopaminereceptor;learningandmemoryX,,,,,,30,:,,Tourette,,,1,,(),(TH)3,42(l2DOPA),DOPA80%:(1);(2);(3);(4)(SNC),(),,504ChinJNeurosci2003November,19(6)X[]100820872(2003)0620405206[]R981;R338[]A[]2003205220[][]020261643275[E2mail][e-mail][](19712),,,,.(VTA),VTA,()(OT),,,,2,(72GM)G[1](DA2R),,D1D2D1D1D5(D1AD1B)D2D2,D3D4C,[2]D1D2,:D1SCH223390SKF238393D1D53DA2Rs,D22RcDNAcDNA1245,415,D2S(D2short),D2,(,,,,)(,),D2L(D2long)D28,7,29D2LD2S[3]D2,D3446,cDNAD3[3]D45,387D42R487D2,D1(D1D5)DA2RTATACAAT[4],D22R(RARE),D1D24,mRNAsD1D2D12R(CPu),(Acb),(OT),(Cx)[3],D1CallejaD1,mRNA:D12RD52RD12R,,D22RmRNACPu,OTAcb(VTA),,D22R,D1[5]D2mRNAD2L,D22RmRNA,,D32RmRNACallija,,,D32R,,,,,D42RmRNA[3]D1D5,,,[6\D1D5,,:D1D5,D1,D5[6],D1;,[7],D1D5GABAD5:D1,D1D5,D1D5[6,7]D1604200311196ChinJNeurosci,November2003,19(6),D5:D1D5,D1D1D5,:D2,D1D2[7]D2,,D2D4,GABA,D4GABAD4,GABA[8]5,GTP2G2,D2LGi22D2S5.1D1(cAMP)A(PKA),PKA,,G,D2(AC)D2cAMPD22RAC,(PTX)D32RcAMP,D22R,D42RcAMP5.2GH4CI,D12RPKA,L2Ca2+,N2P2Ca2+,,D12RT2Ca2+D12RcAMPD2Gi/0D2LD2SG0Ca2+D22RGiN2Ca2+,D22RCa2+D22R,Ca2+THCa2+/(CaMCaM),CaMCa2+2D1D1AMP2,(,,,NG108215)D22RD2LD2SG5.3,D22R(AA)Ca2+,D22RCHOAA,D12RAAPTX,D22RD1D22R:D22RAA,D12R[3]66.1,:,,,,D1D2D1D2(D124),D12R,[9]D22R,,[10]D32R,D32RD42R6.2,,(DAT),,,,,,[11]704,,,D1D22R,,,D2quinpirole(bromocriptine),D12R,,D22RD32RD42R,,6.3,A10[12]Watanabe[13]DaCunha[14],MPTP,,Phillips[15],,,Rosenkranz[16],D1D2D12R(PFC)Sawaguchi[17]DAsulpirdeSCH23390PFC,DAPFCKozlov[18]D12R,El2Ghundi[19]D12RYD1,,,D1,Baldwin[20],,D12RNMDA2R,,D12RNMDA2R,Wilkerson[21],D22R,,D22RUmegaki[22]14T(),D22R,,D22RGreba[23]D22RSmith[24],D22R,,D2L2/2,D2L2RD2D32R,,METH(metaphetamine),D22RD12R,D22R,;D22R,,6.4,,PET,,,Wi,,,DekeyserJ[25]D12R,HembySE[26]RNAcDNA,CA1D12D5mRNA6.5(LTP)Mana2han2Vaughan[27],,,D2remoxiprideLTP(4h),D2LTP,804200311196ChinJNeurosci,November2003,19(6)D1/D5LTP7,D15,G,,,,,,,,,,;,,[][1]GingrichJA,CaronMG.Rcecntadvancesinthemolecularbiolo2gyofdopaminereceptor[J].AnnuRevNeurosci,1993,16:2992321.[2]NgGY,MoillacB,GeorgeSR,etal.Desensitizationphosphory2lationandpalmitoylationofthehumandopamineD1receptor[J].EurJPharmacol,1994,267(1):7219.[3]JacksonDM,Westlind2DanielssonA.Dopaminereceptors:molecularbiology,biochemistryandbehaviouralaspects[J].PharmacolTher,1994,64(2):2912370.[4]ValdenaireO,VernierP,MausM,etal.Transcriptionoftheratdopamine2D22receptorgenefromtwopromoters[J].EurJBiochem,1994,220(2):5772584.[5]CivelliO,BunzowJR,GrandyDK,etal.Molecularbiologyofthedopaminereceptors[J].EurJPharmacol,1991,207(4):2772286.[6]SmileyJF,AILevey,BJCiliax,etal.D1dopaminereceptorim2munoreactivityinhumanandmonkeycerebralcortex:predomi2nantandextrasynapticlocalizationindendriticspines[J].ProcNatlAcadSciUSA,1994,91(12):572025724.[7]LeveyAI,HerschSM,RyeDB,etal.LocalizationofD1andspiperoneandinGH3cellsthatexpressaD22likereceptorwithanunusuallowaffinityforhaloperidolinresponsetoNGF.D2dopaminereceptorsinbrainwithsubtype2specificantibodies[J].ProcNatlAcadSciUSA,1993,90(19):886128865.[8]MrzlakL,BergsonC,PappyM,etal.LocalizationofdopamineD4receptorsinGABAergicneuronsoftheprimatebrain[J].Na2ture,1996,381(6579):2452248.[9]XuM,MratallaR,GoldLH,etal.DopamineD1receptormu2tantmicearedeficientinstriatalexpressionofdynorphinandindopamine2mediatedbehavioralresponses[J].Cell,1994,79(4):7292742.[10]BaikJH,PicettiR,SaiardiA,etal.Parkinsonian2likelocomotorimpairmentinmicelackingdopamineD2receptors[J].Nature,1995,377(6548):4242428.[11]WiseRA.Neurobiologyofaddiction[J].CurrOpinNeurobiol,1996,6(2):2432251.[12]SchultzW,ApicellaP,LjungbergT.Responsesofmonkeydopamineneuronstorewardandconditionedstimuliduringsucces2sivestepsoflearningadelayedresponsetask[J].JNeurosci,1993,13(3):9002913.[13]WatanabeM,KodamaT,HikosakaK.Increaseofextracellulardopamineinprimateprefrontalcortexduringaworkingmemorytask[J].JNeurophysiol,1997,78(5):279522798.[14]DaCunhaC,WietzikoskiS,WietzikoskiEC,etal.Evidenceforthesubstantianigraparscompactaasanessentialcomponentofamemorysystemindependentofthehippocampalmemorysystem[J].NeurobiolLearnMem,2003,79(3):2362242.[15]PhillipsGD,SetzuE,VuglerA,etal.Immunohistochemicalas2sessmentofmesotelencephalicdopamineactivityduringtheacqui2sitionandexpressionofPavlovianversusinstrumentalbehaviours[J].Neuroscience,2003,117