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2002 Fiscal Year Annual Research Report

脳幹シナプス前ATP受容体による神経伝達物質放出制御機構の解明

Research Project

Project/Area Number 13680902
Research InstitutionJikei University School of Medicine

Principal Investigator

加藤 総夫  東京慈恵会医科大学, 医学部, 助教授 (20169519)

KeywordsP2X受容体 / アデノシン5'-三リン酸 / 孤束核 / 興奮性シナプス後電流 / パッチクランプ / シナプス伝達 / 延髄スライス / シナプス前受容体
Research Abstract

ラットおよびマウス延髄スライスを作成し、孤束核小型ニューロンからホールセル・パッチクランプ法で微小興奮性シナプス後電流(mEPSC)を記録した。昨年度は、(1)ATPおよびα,β-methyleneATP(α,βmeATP)がmEPSC頻度を約400%まで有意に増加、(2)この効果は10-40μMのPPADS、1.01-μMのTNP-ATPによって消失、(3)この効果は、細胞外Ca除去によって消失しCd^<2+>存在下に残存、および、(4)α,βmeATPは、孤束刺激誘発EPSCのfailure rataを増大しない事実を証明した。
本年度は、さらに以下の知見を得た。(1)α,βmeATP投与によって80%のニューロンにおいて自発性のものよりも高振幅のmEPSC(large mini)が発生した、(2)cyclopiazonic acid, ryanodine,2APBはこのlarge miniの発現に影響を及ぼさなかった、(3)これらのlarge miniは、Cd^<2+>存在下でも発生し、Cd^<2+>存在下TTX非存在下にシナプス後ニューロンに活動電位を発生させた、(4)α,βmeATPは孤束核ニューロンの自発ならびに微小抑制性シナプス後電流には影響を及ぼさなかった。さらに、マウスにおいて、(5)α,βmeATPによるmEPSC頻度増加は、GAD67陰性細胞のすべてで生じ、GAD67陽性細胞では50%でしか生じなかった。以上から、孤束核興奮性および一部の抑制性小型ニューロンに投射する興奮性ニューロン線維の終末にはP2X受容体(P2X_<4/6>、P2X_<1/5>型もしくは未同定のヘテロ受容体)が発現し、その活性化はP2X受容体からの直接的Ca流入によって、活動電位および電位依存性Caチャネル活性化に依存しないグルタミン酸放出を誘発し、シナプス伝達を誘発する事実が証明された。

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Nishi H, Kato F, Masaki E, Kawamura M: "ADP-sensitive purinoceptors induce steroidogenesis via adenylyl cyclase activation in bovine adrenocortical fasciculata cells"Brit J Pharmacol. 137. 177-184 (2002)

  • [Publications] Kawamura M, Masaki E, Kato F: "Differential enhancement by distinct cholinergic receptors of GABA-and glycine-mediated inhibitory transmissions in the brainstem nociceptive network"Jpn J Pharmacol. 88. 240 (2002)

  • [Publications] Yamazaki K, Masaki E, Kato F: "Effects of sevoflurane on heterologously expressed central-type P2X receptors"Jpn J Pharmacol. 88. 212P (2002)

  • [Publications] Shigetomi E, Kato F: "Large miniature EPSCs upon activation of presynaptic P2X receptors in the nucleus of the solitary tract of rat"7th International symposium on Adenosine and Adenine Nucleotides. (Abstract). 96 (2002)

  • [Publications] Kato F, Shigetomi E: "Activation of P2X receptors elicits large-amplitude miniature excitatory postsynaptic currents In the nucleus of the solitary tract of the rat"3rd Forum of European Neuroscience. (Abstracts). 113.7 (2002)

  • [Publications] Shigetomi E, Kato F: "Activation of P2X receptors facilitates excitatory, but not inhibitory, synaptic transmission in the nucleus of the solitary tract of the rat"Abstract Viewer/Itinerary Planner. Washington, DC : Society for Neuroscience. 549.13 (2002)

  • [Publications] Fukuda S, Kato F, Yamaguchi T, Miyamoto Y, Hisatsune T: "Passive membrane properties of neural stem cells from the adult nestin -GFP mouse dentate gyrus"Abstract Viewer/Itinerary Planner. Washington, DC : Society for Neuroscience. 127.5 (2002)

  • [Publications] Kato F, Kawamura M, Tanaka J: "Bi-modal regulation of neuronal excitability by extracellular ATP through activation of distinct purinoceptors in the hippocampus"The 3rd International Symposium on the Study of Brain Function. (Abstracts). 56 (2002)

  • [Publications] Shigetomi E, Kato F: "Origin of glutamate release by activation of presynaptic P2X receptors in the nucleus tractus solitarii of the rat"The 3rd International Symposium on the Study of Brain Function. (Abstracts). 210 (2002)

  • [Publications] Kawamura M, Masaki E, Kato F: "Regulation of inhibitory synaptic transmission by cholinoceptors in the brainstem nociceptive network of the rat"The 3rd International Symposium on the Study of Brain Function. 213 (2002)

  • [Publications] 加藤総夫: "「一粒で二度おいしい」細胞外メッセンジャーとしてのATP-細胞外ATPとプリン受容体による脳内シナプス伝達の多重制御"赤池, 東, 久保編,脳機能の解明 生命科学の主潮流,ガイア出版会・九州大学大学院医学研究院. 78-81 (2002)

  • [Publications] 加藤総夫, 繁富英治, 川村将仁, 池田 亮: "能幹スライスにおけるパッチクランプ法を用いた脳幹ネットワークのシナプス伝達解析法"日本薬理学雑誌. 121. 255-263 (2003)

  • [Publications] Kawamura K, Tanaka J, Inoue K, Kato F: "Opposite responses of EPSC and IPSC to ATP of the CA3 pyramidal neurons In the rat hippocampus slices"Neuroscience Research. Suppl 25. S177 (2001)

  • [Publications] Shigetomi E, Kato F: "Little Involvement of calcium release from Intracellular stores In the ATP-activated 'Iarge-and fast minis' miniature EPSCs In the nucleus of the solitary tract"Neuroscience Research. Suppl 25. S177 (2001)

  • [Publications] Takano K, Kato F: "Effect of P2X receptor blokade in the nucleus of the solitary tract on the vagal inspiration promoting reflex in rabbits"Jap J Physiol. 52 Suppl. S89 (2002)

  • [Publications] Kato F, Shigetomi E: "Large-amplitude miniature EPSCs upon activation of presynaptic P2X receptors in the nucleus of the solitary tract"Jap J Physiol. 52 Suppl. S137 (2003)

  • [Publications] Kato F, Shigetomi E, Takano K: "Possible involvement of P2X receptors in the nucleus of the solitary tract in the central respiratory control"J Pharmacol Sci. 91 Suppl. 183 (2003)

  • [Publications] Yamazaki K, Shigetomi E, Kata F: "Pharmacological identification of the type of voltage-gated calcium channels underlying glutamate release from primary afferents in the nucleus tractus solitarii of the mouse"J Pharmacol Sci. 91 Suppl. 180 (2003)

  • [Publications] Kawamura M, Kato F: "Modulation of hippocampal network activity through distinct purinergic mechanisms in the rat"J Pharmacol Sci. 91 Suppl. 56 (2003)

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Published: 2004-04-07   Modified: 2016-04-21  

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