脳内生理活性物質の長期効果と情報伝達機構

1993 年度 実績報告書

• 研究課題/領域番号: 04304037
• 研究機関: 放送大学
• 研究代表者: 鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)
• 研究分担者: 遠山 正彌 大阪大学, 医学部, 教授 (40028593) ; 米田 幸雄 摂南大学, 薬学部, 助教授 (50094454) ; 栗山 欣彌 京都府立医科大学, 教授 (20079734) ; 佐藤 公道 京都大学, 薬学部, 教授 (80025709) ; 野村 靖幸 北海道大学, 薬学部, 教授 (00034041)
• キーワード: dexamethasone / NO 合成酵素 / 長期増強 / DBI mRNA / Myc / CABA^A受容体 / サブスタンスP / キナーゼIV

研究概要

ラット海馬培養神経細胞にdexamethasoneはカイニン酸による細胞毒性を増強させるが、この増強をニコチンが用量依存的に抑制することを認めた(鬼頭)。
グリア細胞にLPSを作用させるとチロシン蛋白質のリン酸化を介し、NO合成酵素(NOS)が誘導されることを示した(野村)。
苔状線維-CA3野錘体細胞シナプスにおける長期増強がムスカリン性M_1及びM_2受容体によって各々促進的及び抑制的に調節されていることを明らかにした(佐藤)。
ラットのアルコール依存形成時には脳内におけるendozepine(diazepam binding inhibitor: DBI)mRNA発現の明らかな上昇を認めた(栗山)。
マウス脳核抽出液中の転写制御因子Myc結合活性は、ピロリン酸の添加により濃度依存的に増強された(米田)。
脊髄後角でのGABA_A受容体gamma_1、gamma_2サブユニットを発現する細胞は主として投射ニューロンであり、AMPA型受容体G1uR1,2を発現する細胞は主として介在ニューロンであることを明かにした(遠山)。
神経ペプチドのサブスタンス(SP)受容体をコードするmRNAの特定部位に対して、アンチセンスDNAを合成し、ヒト脳アストロサイトーマ(U-87MG細胞)に添加した。その結果、SP受容体量の減少が認められた(仲田)。
ラット海馬の遺伝子発現に及ぼすペンチレンテトラゾール(PTZ),カイニン酸(KA)全身的投与の効果を調べた。PTZはc-fosのKAはエンケファリンのmRNA量を増加するがコレシストキニン遺伝子の発現はこれらの薬物によって変動しなかった(村木)。
免疫抑制薬cyclosporin Aの慢性末梢投与はcyclosporin結合タンパクの脳内mRNAをdown-regulateした(小川)。
カルモデュリン依存性蛋白質リン酸化酵素、IV(キナーゼIV)のcDNAを大腸菌に導入して発現させると不活性なキナーゼIVが生産されるが、この不活性なキナーゼIVを活性化する蛋白因子が脳に特異的に存在することを見出した(藤澤)。

研究成果

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