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D1 D2 D3 D4 D5

D1 D2 D3 D4 D5 Coding sequence 464AA D2A 443,400AA 400AA 387AA 477AA D2B 414AA

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D1 D2 D3 D4 D5

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  1. D1 D2 D3 D4 D5 Coding sequence 464AA D2A 443,400AA 400AA 387AA 477AA D2B 414AA Chromosome 5q31-q34 11q22-q23 3q13.3 11p 4p16.3 Highest density Neostriatum Neostriatum Paleostriatum Medulla Hypothalamus Frontal cortex Hippocampus Pituitary No Yes No ? No DA neuron(A9,10) No Yes Yes ? ? Affinity for DA micromolar micromolar nanomolar submicromolar submicromolar Agonist SKF-38393 Bromocriptine 7-OH-DPAT ? SKF-38393 Antagonist SCH-23390 Haloperidol UH 232 clozapine SCH-23390 Adenylyl cyclase stimulate inhibit ? inhibit stimulate AA release potentiate stimulate ? ? ? 도파민 수용체

  2. 세로토닌 수용체 Superfamily G-protein coupled Ion channel Family Serotonin Subfamily 5-HT1 5-HT2 5-HT4 5-HT3 Subtypes 5-HT1A 5-HT2A 5-HT? 5-HT1B 5-HT2C 5-HT1D Second decrease PI increase ligand gated Messenger cAMP hydrolysis cAMP Ion channel

  3. 무스카린 수용체 Molecular subtype m1 m2 m3 m4 m5 Pharmacological 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

  4. 니코틴 수용체 Ligand binding Subtype distribution Region Nicotine BgT a2 a3 a4 a5 a6 a7 b2 b3 b4 Forebrain Cortex +++ ++ ++ +++ + + + Hippocampus +++ + ++ ++ +++ ++ ++ Thalamus +++ ++ +++ ++ + +++ ++ ++ Hypothalamus + +++ + + ++ + + Amygdala ++ ++ + + Septum ++ ++ + + Brainstem Motor nuclei ++ +++ + ++ + ++ LC ++ ++ +++ + ++ + IPN +++ +++ +++ + + ++ ++ ++ Cerebellum + + ++ + ++ a1,b1 muscle type a=alpha, b=beta

  5. NMDA 수용체

  6. GABA 수용체

  7. GABAA-benzodiazepine receptor complex

  8. NH2 204 113 207 COOH GTP • -adrenoceptor adenylate cyclase Fig 13. G-protein coupled receptor and G-protein G- 단백질 배위자 수용체 전달기 효과기

  9. G 단백질

  10. G 단백질 효과기 • Adenylate & guanylate cyclase • Phospholipase C & A2 • Phosphodiesterase • K+ & Ca++ channels • Others

  11. Adenylate Guanylate Phospho- Phospho- cyclase cyclase lipase C lipase A2 cAMP cGMP IP3 DG AA Ca++ Eicosanoids PKA PKG PKC Cellular responses

  12. 이차전령 AC cAMP PLC IP3,Ca PLC DG PLA2 AAs(Arachidonic acids) Protein kinase A Ca/Cam Kinase Protein Kinase C Tyrosine Kinase Neurotransmitters Cell membraine Nucleus IEGs G receptors

  13. 신경신호전달계 1 5-HT1A 5-HT2A R R AC PLC PIP2 I IP3 ATP cAMP DG IP1 IP2 Calmodulin dependent PK PKA PKC IEG c-fos Structural gene Fig 14. Major signal transduction pathways

  14. Receptor tyrosine kinase P Ras P P P P Grb P GTP GDP Sos Raf Transcrition factor phosphorylation MAPKK Gene transcription MAPK Mitogen-activated protein kinase protein synthesis Fig 15. Tyrosine kinase signaling 신경신호전달계 II

  15. Protein Kinase A

  16. The phospholipase C

  17. Arach idonic acids 와 Eicosanoids

  18. Arachdonic acids 와 Eicosanoids

  19. R R Gs AC Gq PLC Synaptic regeneration/remodeling Sos MAP kinase kinase MAP kinase cAMP IP3 PKA Ca++ dependent protein kinase RAS Raf Grb Neurotrophic factor CREB BDNF & trkB trk Protein kinases

  20. 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

  21. 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

  22. 환경(경험)과 뇌 신경가소성 : 뇌의 적응

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