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ＧＡＢＡ Ａ　 Receptor の役割と疾患

ＧＡＢＡ Ａ　 Receptor の役割と疾患. 040924 41057 Tamiya H. 抑制性 transmitter. Ｗｈａｔ　ｉｓ　ＧＡＢＡ？. one-third of the synapses in the brain use commonly found in local circuit interneurons Purkinje cells provide an example of a GABAergic projection neuron. GABA’s receptor. Cycle of GABA. ２　ＧＡＢＡ A R と薬剤.

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ＧＡＢＡ Ａ　 Receptor の役割と疾患

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  1. ＧＡＢＡＡ　Receptorの役割と疾患 040924 41057 Tamiya H

  2. 抑制性transmitter

  3. Ｗｈａｔ　ｉｓ　ＧＡＢＡ？ • one-third of the synapses in the brain use • commonly found in local circuit interneurons • Purkinje cells provide an example of a GABAergic projection neuron

  4. GABA’s receptor

  5. Cycle of GABA

  6. ２　ＧＡＢＡARと薬剤

  7. ＧＡＢＡa target　の薬剤 • plant alkaloids bicuculline （Dutchman‘s breeches） picrotoxin (Anamerta cocculus ) • Dieldrin, a commercial insecticide ⇒block , powerful CNS stimulants. • Muscimol (a mushroom), hallucinogen ⇒Activates, a powerful depressant

  8. ＧＡＢＡ薬剤の作用部位 • pore domain ー barbiturates（催眠薬） neurosteroid picrotoxin (antagonist) • outside the pore Benzodiazepines　（抗不安薬） 　（diazepam (Valium) ,chlordiazepoxide (Librium))

  9. ＧＡＢＡとalcohol • Enhance GABAA ＆ glycine receptor • some aspects of drunken behavior • 45aa（特に２aa)がallostericに必要十分 Nature 389, 385-389, 1997

  10. アルコールの作用について

  11. ３　抑制性シナプスの働き

  12. reciprocal innervation • 拮抗しあう筋を制御する回路 • 興奮性ニューロンと抑制性ニューロン(介在ニューロン) • 拮抗しあう筋の活動にコントラストをつける • InterneuronはＧＡＢＡ、glycine両方で制御 • Strychnine(殺鼠剤）

  13. ＧＡＢＡa receptorの働き • Controlling the excitability of the brain • Modulation of anxiety • Feeding and drinking behavior • Circadian rhythms • Cognition, vigilance, memory, learning

  14. Circadian rhythm • Suprachiasmatic nucleusが担う • firing rateが昼は高く、夜は低い • ＧＡＢＡは昼excitatory,夜はinhibitory 　　　（細胞内chloride濃度によると考えられる） ⇒firing rate の振動を増幅している？ Ｎａｔｕｒｅ　３８７　５９８－６０３　（１９９７）

  15. ＧＡＢＡ作用の変化

  16. 注意！！ • ＥＰＳＰとはaction potentialを発生させやすい方向に向かわせるもの • Threshold よりもＥrevが高くない 　　　　⇒膜電位が上がってもIPSP • Conductance↑⇒膜電位は動きにくく

  17. ５ＧＡＢＡＡＲ関連疾患

  18. Stiff man syndrome • GADへの自己免疫 • Chronic rigidity　（慢性硬直）, spasm (痙攣） • Gephyrin　（GABAA,GlyRとassociate)、が原因の場合も • 腫瘍随伴性（共有分子への自己抗体） • Benzodiazepin, baclofen etc.で対症

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