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