多巴胺受体的结构和功能-李凡

·　　·李凡,舒斯云,包新民(,,510280)[]　。。,,Tourette,。,,[]　;;StructureandfunctionofdopaminereceptorsLIFan,SHUSi-yun,BAOXin-min(InstituteforNeuroscienceofFirstMilitaryMedicalUniversity,ZhujiangHospital,Guangzhou510280,China)[Abstract]　Dopamine(DA)isthemostabundantcatecholaminergicneurotransmitterinthebrain.TheinvolvementandimportanceofDAasaneurotransmitterintheregulationofdifferentphysiologicalfunctionsinthecentralnervoussys-tem(CNS)arewellknow.DeregulationofthedopaminergicsystemhasbeenlinkedwithParkinsondisease,Tourettesyndrome,schizophrenia,attentiondeficithyperactivedisorder(ADHD)andgenerationofpituitarytumours.Thisreviewfocusesonthepharmacologicalandbiochemicalfeaturessharedbythedopaminereceptors.Thedistributionofthediffer-entdopaminereceptorsintheCNSandtheirfunctionespeciallyassociatedwithlearningandmemoryareemphasized.[Keywords]　dopamine;dopaminereceptor;learningandmemory,,,,,,。30,:,,Tourette,。,,。1　,,()。,。(TH)3,4-(l-DOPA),DOPA。80%。:(1);(2);(3);(4)。(SNC),()。,,405中国神经科学杂志ChinJNeurosci　2003　November,19(6)[]　1008-0872(2003)06-0405-06　　[]　R981;R338　　[]　A　　[]　2003-05-20[]　　　[]　020-61643275　　[E-mail]　[e-mail]　　[]　(1971-),,,,.。(VTA),。。VTA,()、(OT)。。,,,,。2,(7-GM)G[1]。(DA-R),,D1D2。D1D1D5(D1AD1B)。D2D2,D3D4。C,[2]。D1D2,。:D1SCH-23390SKF-38393D1D5。。。3DA-Rs,D2-RcDNA。cDNA1245,415,D2S(D2short),D2。,(,,,,)(,),D2L(D2long)。D28,7。,29D2LD2S[3]。D2,。D3446,cDNA。D3[3]。D45,387。。D4-R487。D2,D1(D1D5)。DA-RTATACAAT[4],。D2-R(RARE),D1D2。4,mRNAs。D1D2。D1-R(CPu),(Acb),(OT),(Cx)[3]。,D1Calleja。D1,mRNA。:D1-R。D5-RD1-R,,。D2-RmRNACPu,OTAcb。(VTA),,D2-R。,D1[5]。D2mRNAD2L。,D2-RmRNA,,。D3-RmRNACallija,,,。D3-R,。,,,,D4-RmRNA[3]。。D1D5,,,[6〗。D1D5,,。:D1D5,D1,D5[6]。,D1;,[7]。,D1D5GABA。D5。:D1,D1D5,D1D5[6,7]。D1406中国神经科学杂志　200311　19　6　ChinJNeurosci,November2003,19(6),D5。:D1D5,D1。D1D5,。:D2,。D1。D2[7]。D2,,。D2。D4,GABA。,D4GABA。D4,GABA[8]。5,。GTP-。G-。,D2LGi-2αD2S。5.1　　D1(cAMP)。A(PKA),PKA,,G,。D2(AC)。D2cAMP。D2-RAC,(PTX)。D3-RcAMP,D2-R。,D4-RcAMP。5.2　GH4CI,D1-RPKA,L-Ca2+,N-P-Ca2+。,,D1-RT-Ca2+。D1-RcAMP。D2Gi/0α。D2LD2SG0αCa2+。D2-RGiαN-Ca2+,D2-RCa2+。D2-R,Ca2+。THCa2+/(CaMCaMⅡ),CaMⅡCa2+-。D1。D1AMP-,。(,,,NG108-15)D2-R。D2LD2SG。5.3　,D2-R(AA)。Ca2+,D2-RCHOAA,D1-R。AAPTX,D2-R。D1D2-R:D2-RAA,D1-R[3]。66.1　,。:,,,。,。D1D2。D1D2。(D1-4)。,D1-R,[9]。D2-R,,[10]。D3-R,D3-R。D4-R。6.2,,。(DAT),。,,,,,[11]。407,,　,D1D2-R,,。,D2quinpirole(bromocriptine),。D1-R,。,D2-R。D3-R。D4-R,,。6.3　。,A10[12]。Watanabe[13]。DaCunha[14],MPTP,,。Phillips[15],,,。Rosenkranz[16],。D1D2。D1-R(PFC)。Sawaguchi[17]DAsulpirdeSCH23390PFC,DAPFC。Kozlov[18]D1-R,。El-Ghundi[19]D1-RY。D1,,,D1,。Baldwin[20],,D1-RNMDA-R,,D1-RNMDA-R,。Wilkerson[21],D2-R,,D2-R。Umegaki[22]14T(),D2-R,,D2-R。Greba[23]D2-R。Smith[24],D2-R,,。D2L-/-,D2L-R。D2D3-R,,METH(metaphetamine),D2-RD1-R。,D2-R,;D2-R,,。6.4　,,。PET,,,Wi,,,。DekeyserJ[25]D1-R,。HembySE[26]RNAcDNA,CA1D1-D5mRNA。6.5(LTP)。Mana-han-Vaughan[27],,,D2remoxiprideLTP(4h),D2LTP。,408中国神经科学杂志　200311　19　6　ChinJNeurosci,November2003,19(6)D1/D5LTP。7,。D1～5,G。,,,。,,,,,,。,;,,。[][1]　GingrichJA,CaronMG.Rcecntadvancesinthemolecularbiolo-gyofdopaminereceptor[J].AnnuRevNeurosci,1993,16:299-321.[2]　NgGY,MoillacB,GeorgeSR,etal.Desensitizationphosphory-lationandpalmitoylationofthehumandopamineD1receptor[J].EurJPharmacol,1994,267(1):7-19.[3]　JacksonDM,Westlind-DanielssonA.Dopaminereceptors:molecularbiology,biochemistryandbehaviouralaspects[J].PharmacolTher,1994,64(2):291-370.[4]　ValdenaireO,VernierP,MausM,etal.Transcriptionoftheratdopamine-D2-receptorgenefromtwopromoters[J].EurJBiochem,1994,220(2):577-584.[5]　CivelliO,BunzowJR,GrandyDK,etal.Molecularbiologyofthedopaminereceptors[J].EurJPharmacol,1991,207(4):277-286.[6]　SmileyJF,AILevey,BJCiliax,etal.D1dopaminereceptorim-munoreactivityinhumanandmonkeycerebralcortex:predomi-nantandextrasynapticlocalizationindendriticspines[J].ProcNatlAcadSciUSA,1994,91(12):5720-5724.[7]　LeveyAI,HerschSM,RyeDB,etal.LocalizationofD1andspiperoneandinGH3cellsthatexpressaD2-likereceptorwithanunusuallowaffinityforhaloperidolinresponsetoNGF.D2dopaminereceptorsinbrainwithsubtype-specificantibodies[J].ProcNatlAcadSciUSA,1993,90(19):8861-8865.[8]　MrzlakL,BergsonC,PappyM,etal.LocalizationofdopamineD4receptorsinGABAergicneuronsoftheprimatebrain[J].Na-ture,1996,381(6579):245-248.[9]　XuM,MratallaR,GoldLH,etal.DopamineD1receptormu-tantmicearedeficientinstriatalexpressionofdynorphinandindopamine-mediatedbehavioralresponses[J].Cell,1994,79(4):729-742.[10]BaikJH,PicettiR,SaiardiA,etal.Parkinsonian-likelocomotorimpairmentinmicelackingdopamineD2receptors[J].Nature,1995,377(6548):424-428.[11]WiseRA.Neurobiologyofaddiction[J].CurrOpinNeurobiol,1996,6(2):243-251.[12]SchultzW,ApicellaP,LjungbergT.Responsesofmonkeydopamineneuronstorewardandconditionedstimuliduringsucces-sivestepsoflearningadelayedresponsetask[J].JNeurosci,1993,13(3):900-913.[13]WatanabeM,KodamaT,HikosakaK.Increaseofextracellulardopamineinprimateprefrontalcortexduringaworkingmemorytask[J].JNeurophysiol,1997,78(5):2795-2798.[14]DaCunhaC,WietzikoskiS,WietzikoskiEC,etal.Evidenceforthesubstantianigraparscompactaasanessentialcomponentofamemorysystemindependentofthehippocampalmemo