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D1 D2 D3 D4 D5Coding sequence 464AA D2A 443,400AA 400AA 387AA 477AA D2B 414AA Chromosome 5q31-q34 11q22-q23 3q13.3 11p 4p16.3Highest density Neostriatum Neostriatum Paleostriatum Medulla Hypothalamus Frontal cortex HippocampusPituitary No Yes No ? NoDA neuron(A9,10) No Yes Yes ? ?Affinity for DA micromolar micromolar nanomolar submicromolar submicromolarAgonist SKF-38393 Bromocriptine 7-OH-DPAT ? SKF-38393Antagonist SCH-23390 Haloperidol UH 232 clozapine SCH-23390Adenylyl cyclase stimulate inhibit ? inhibit stimulateAA release potentiate stimulate ? ? ?
도파민 수용체
세로토닌 수용체
Superfamily G-protein coupled Ion channelFamily SerotoninSubfamily 5-HT1 5-HT2 5-HT4 5-HT3Subtypes 5-HT1A 5-HT2A 5-HT? 5-HT1B 5-HT2C 5-HT1D Second decrease PI increase ligand gatedMessenger cAMP hydrolysis cAMP Ion channel
무스카린 수용체
Molecular subtype m1 m2 m3 m4 m5Pharmacological subtype M1 M2 M3 M4 -
Tissue distribution brain heart exocrine brain brain grand
exorcrine brain brain gland smooth smooth brain muscle
Biochemical response IP3 cAMP IP3 cAMP IP3
Selective antagonist Pirenzepine Telenzepeitne
니코틴 수용체
Ligand binding Subtype distributionRegion Nicotine BgT a2 a3 a4 a5 a6 a7 b2 b3 b4ForebrainCortex +++ ++ ++ +++ + + +Hippocampus +++ + ++ ++ +++ ++ ++Thalamus +++ ++ +++ ++ + +++ ++ ++Hypothalamus + +++ + + ++ + +Amygdala ++ ++ + +Septum ++ ++ + +Brainstem Motor nuclei ++ +++ + ++ + ++ LC ++ ++ +++ + ++ +IPN +++ +++ +++ + + ++ ++ ++ Cerebellum + + ++ + ++a1,b1 muscle type a=alpha, b=beta
NMDA 수용체
GABA 수용체
GABAA-benzodiazepine receptor complex
NH2
COOH
113204207
-adrenoceptor adenylate cyclaseGTP
Fig 13. G-protein coupled receptor and G-protein
G- 단백질
배위자 수용체 전달기 효과기
G 단백질
G 단백질 효과기 Adenylate & guanylate cyclase Phospholipase C & A2
Phosphodiesterase K+ & Ca++ channels Others
Adenylate Guanylate Phospho- Phospho-cyclase cyclase lipase C lipase A2
cAMP cGMP IP3 DG AA
Ca++ Eicosanoids
PKA PKG PKC
Cellular responses
Cell m
emb
raine
Neu
rotransm
itters
receptorsG
Protein kinase A
Ca/Cam Kinase
Protein Kinase C
Tyrosine Kinase
Nucleus
IEGs
AC cAMP
PLC IP3,Ca
PLC DG
PLA2 AAs(Arachidonic acids)
이차전령
ATP cAMP
PKA
R
PIP2
R
AC PLC
5-HT2A5-HT1A
DG
PKCCalmodulin dependent PK
IEG
Structural gene
c-fos
IP3
IP2IP1
I
Fig 14. Major signal transduction pathways
신경신호전달계 1
Fig 15. Tyrosine kinase signaling
PPP
PPP
GrbSos
Ras
GTP GDP
Raf
MAPKK
MAPK
Mitogen-activated protein kinase
Transcrition factor phosphorylation
Gene transcription
protein synthesis
Receptor tyrosine kinase신경신호전달계 II
Protein Kinase A
The phospholipase C
Arach idonic acids 와 Eicosanoids
Arachdonic acids 와 Eicosanoids
R GsAC R GqPLC
cAMP IP3
PKA Ca++ dependent protein kinase
CREB
BDNF & trkBN
eurotrophic factor trk
Sos
Grb
RAS Raf
MAP kinase kinas
e
MAP kinas
e
Protein kinases
Syn
ap
tic
reg
en
era
tion
/rem
od
elin
g
세포 반응•Rapid mediatory process activation / inhibition of ion channels•Short-term mediatory process general metabolism neurotransmitter synthesis/release receptor sensitivity membrane potential short-term memory•Long-term mediatory process(via gene expression) Synthesis of channel, receptor, second messenger Synaptogenesis Learning and memory
도파민 : 정신분열병 , 기분장애 파킨슨병 추체외로증상 항정신병약물 작용기전 약물중독
노르에피네프린 기분장애 공황장애 공포 항우울제 작용기전
세로토닌 불안 , 우울증 항우울제 작용기전
아세틸콜린 기억장애 알쯔하이머병
GABA 간질 신경안정제 작용기전
NMDA 학습과 기억 정신분열병 신경독성과 세포사망
엔도르핀 통증 , 기분 , 보상
신경가소성 : 뇌의 적응
환경 ( 경험 ) 과 뇌