1992 年度実績報告書

脳内生理活性物質の長期効果と情報伝達機構

研究課題

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, 医学部, 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	c-fos / 長期増強 / GABAAα1サブユニットmRNA / AP-1 / interleukin-1β / zif / 268 / カイネースIV
研究概要	(1)ラット海馬におけるin vivo dialysis実験によりミネラルコルチコイドが各種アミノ酸性伝達物質、アセチルコリンの遊離に影響を与えることを見いだした。(2)P1代謝に共役するm1、m3両ムスカリン性アセチルコリン受容体(MusR)刺激のc-fos誘導作用とその機序について研究し、ジアシルグリセロールがPKCの活性化を介して弱いc-fos誘導を引き起こすことを認めた。(3)ホールセル・クランプ記録により、CA3野錐体細胞内のGTP結合タンパク質機能を抑制した状態では、海馬采線維とのシナプスでの長期増強は顕著に抑制されることを認めた。(4)アルコール依存症モデル動物を用いて、GABA_Aα_1サブユニットmRNAの脳内発現の増加を認めた。(5)NMDAの脳室内投与により、マウス脳細胞核分画抽出液中のAP-1の活性上昇を認めた。(6)GABA_A、ニューロテンシン、グリシン、グルタミン酸などの受容体についてin situ hybridizationにより脳内の個体発生的分布を明らかにした。(7)interleukin-β(IL-1β)をラット側脳室に投与した結果、サブスタンスP受容体およびmRNA量の減少を認めた。(8)ラット脳における遺伝子発現についてnorthern blotting法により検討した。海馬において、けいれん薬ペンチレンテトラゾールは最初期遺伝子c-fosとzif/268の発現を誘導し、これをコレシストキニンが抑制することを見いだした。また、線条体プレプロエンファリン遺伝子及び海馬プレプロコレシストキニン遺伝子の発現が、グルココルチコイドにより調節を受けることを認めた。(9)CCK-8の投与によってcycloheximideによるc-fos mRNA発現が抑制されることを認めた。(10)カイネースIIの活性発現にThr-286の自己燐酸化が重要であることを明らかにした。カイネースIVをラットの脳より精製してその性質を明らかにした。

研究成果
(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] Miyoshi,R.,Kito,S.,Nomoto,T.,: "Cholecystokinin increases intracellular Ca^<2+> concentration in cultured striatal neurons" Neuropeptides. 18. 115-119 (1991)
[文献書誌] Miyoshi,R.,Kito.S.,Nomoto,T.,Weiser,M.,Joh,T.: "Effect of caerulein on expression of the immediate early genes c-fos and zif/268 in the rat brain" Neuroscience Letter. 145. 205-208 (1992)
[文献書誌] Miyoshi,R.,Kito,S.,Tanaka,A.: "Effect of neurotensin on dopamine and muscarinic acetylcholine receptors in the rat striatum" Basal Ganglia III、27. 39. 371-378 (1992)
[文献書誌] Kumsagai,C.,Tohda,M.,Isobe,M.Nomura,Y.: "Involvement of GAP-43 with irreversible neurite outgrowth by dibutyryl cAMP and phorbol ester in NG108-15 cells." J.Neurochem. 59(1). 41-47 (1992)
[文献書誌] Urusihara,H.,Tohda,M.,Nomura,Y.: "Selective potentiation of NMDA-induced currents by protein kinase C in Xenopus oocytes injected with rat brain RNA." J.Biol.Chem.267. 11697-11700 (1992)
[文献書誌] 野村靖幸: "記憶の細胞分子薬理" BIOmedica. 7(7). 708-713 (1992)
[文献書誌] Katuki,H.,Kaneko,S.Sato,M.: "Involvement of postsymaptic in hippocampal long-term potenttlation." Brain Research. 581. 108-114 (1992)
[文献書誌] Ueda,M.,Fujii,T.,Kuraishi,Y.,Satoh,M.: "Bifemelane enhances high K+-evoked release of glutamate from mossy fiber synaptosomes of guinea pig hippocampus." European J.of Parma.219. 271-277 (1992)
[文献書誌] Kaneko,S.,Takahashi,H.,Satoh,M.: "Metabotropic responses to acetylcholine and serotonin of Xenopus oocytes injected with rat brain mRNA are transduced by different G-protein subtypes." FEBS Letters. 299. 179-182 (1992)
[文献書誌] Yoneda,Y.,Ogita,K.: "Attempts to isolate the NMDA receptor complex from rat brain." Mol.Neuropharmacol.2. 65-70 (1992)
[文献書誌] Tamaru,M.,Yoneda,Y.,Ogita,K.,Shimizu,J.,Matsutani,T.,Nagata,Y.: "Excitatory amino acid receptors in brains of rats with methylazoxy-methanol-induced microencephaly." Neurosci.Res.14. 13-25 (1992)
[文献書誌] Yoneda,Y.,Suzuki,T.,Ogita,K.,Han,D.: "Support for rakiolabaeling of a glycine recognition domain on the N-methyl-D-aspartate receptor ionophore complex by [ ^3H]5,7-dichlorokynurenate in rat brain." J.Neurochem.60. 634-645 (1993)
[文献書誌] Araki,T.,Tohyama,M.: "Region-specific expression of GABA_A receptor α_3 and α_4 subunits mRNAs in the rat brain" Mole.Brain Res.,. 12. 293-314 (1992)
[文献書誌] Araki,T.,Kiyama,H.,Tohyama,M.: "The GABA_A receptor γ_1 subunit is expressed by distinct neuronal populations" Mole.Brain Res.15. 121-132 (1992)
[文献書誌] Zhang,J.H.,Sato,M.,Tohyama,M.: "Co-expression of the α_1 and β_2 subunit genes of the GABA_A reaceptor in the magnocellular preoptic nucleus" Mole.Brain Res.15. 171-173 (1992)
[文献書誌] Hirouchi,M.,Hashimoto,T.: "Alteration in expression of GABA_A receptor alphal-subunit nRNA in following continuous ethanol administration" Europ.J.Pharmacol.(1993)
[文献書誌] Mizutani,M.,Hashimoto,T.fNakayasu,H.,Kuriyama,K.: "Alterations in cerebral GABA_B receptor binding during the formation of alcohol dependence." Pharmacology Communications. (1993)
[文献書誌] Hirouchi,H.,Ohkuma,S.,Kuriyama,K.: "Muscimol-induced reduction of GABA_A reaceptor alpha_1-subunit mRNA in in primary cultured neurons" Mole.Brain Res. 15. 327-331 (1992)
[文献書誌] Nakata,Y.,Takamatsu,H.,Kuroyanagi,N.,Nishio.H.,Segawa,T.,Akizawa;,T.: "Isolation of substance P binding protein from rat brain" J.Pharmacol.59. 313-319 (1992)
[文献書誌] Ogo,H.,Kuroyanagi,N.,Nishio,H.,Hirai,Y.,Akiyama,M.,Nakata,Y.: "Characterization of funtional substance P recepjtors in human astrocytoma cell line" J.Pharmacol.(suppl.). 61. 68 (1993)
[文献書誌] Yamawaki,Y.,m Ogawa,N.: "Successful treatment of levodopa-inducednefuroleptic malignant syndrome(NMS)and disseminated intravascular coagulation(DIC)in a patient with Parkinson'disease" Internal Medicine. 31. 1298-1302 (1992)
[文献書誌] Asanuma,M.,Wgawa,N.,Hirata,H.,Chou,H.,Kondo,Y.,Mori,A.: "Ischemia-induced changes in α-tubulin and β-actin mRNA in the gerbil brain and effects of bifemelane hydrochrolide" Brain Res.600. 243-248 (1993)
[文献書誌] 小川紀雄,森昭胤: "パーキンソン病とフリーラジカル" 神経精神薬理. 14. 735-744 (1993)
[文献書誌] Kito,S.,Miyoshi,R.: "Neurotransmitter Receptors:Neuroreceptor Mechanism in Brain" Plenum Press, 495 (1991)

1992 年度 実績報告書

脳内生理活性物質の長期効果と情報伝達機構

研究代表者

鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)

研究成果

[文献書誌] Miyoshi,R.,Kito,S.,Nomoto,T.,: "Cholecystokinin increases intracellular Ca^<2+> concentration in cultured striatal neurons" Neuropeptides. 18. 115-119 (1991)

[文献書誌] Miyoshi,R.,Kito.S.,Nomoto,T.,Weiser,M.,Joh,T.: "Effect of caerulein on expression of the immediate early genes c-fos and zif/268 in the rat brain" Neuroscience Letter. 145. 205-208 (1992)

[文献書誌] Miyoshi,R.,Kito,S.,Tanaka,A.: "Effect of neurotensin on dopamine and muscarinic acetylcholine receptors in the rat striatum" Basal Ganglia III、27. 39. 371-378 (1992)

[文献書誌] Kumsagai,C.,Tohda,M.,Isobe,M.Nomura,Y.: "Involvement of GAP-43 with irreversible neurite outgrowth by dibutyryl cAMP and phorbol ester in NG108-15 cells." J.Neurochem. 59(1). 41-47 (1992)

[文献書誌] Urusihara,H.,Tohda,M.,Nomura,Y.: "Selective potentiation of NMDA-induced currents by protein kinase C in Xenopus oocytes injected with rat brain RNA." J.Biol.Chem.267. 11697-11700 (1992)

[文献書誌] 野村 靖幸: "記憶の細胞分子薬理" BIOmedica. 7(7). 708-713 (1992)

[文献書誌] Katuki,H.,Kaneko,S.Sato,M.: "Involvement of postsymaptic in hippocampal long-term potenttlation." Brain Research. 581. 108-114 (1992)

[文献書誌] Ueda,M.,Fujii,T.,Kuraishi,Y.,Satoh,M.: "Bifemelane enhances high K+-evoked release of glutamate from mossy fiber synaptosomes of guinea pig hippocampus." European J.of Parma.219. 271-277 (1992)

[文献書誌] Kaneko,S.,Takahashi,H.,Satoh,M.: "Metabotropic responses to acetylcholine and serotonin of Xenopus oocytes injected with rat brain mRNA are transduced by different G-protein subtypes." FEBS Letters. 299. 179-182 (1992)

[文献書誌] Yoneda,Y.,Ogita,K.: "Attempts to isolate the NMDA receptor complex from rat brain." Mol.Neuropharmacol.2. 65-70 (1992)

[文献書誌] Tamaru,M.,Yoneda,Y.,Ogita,K.,Shimizu,J.,Matsutani,T.,Nagata,Y.: "Excitatory amino acid receptors in brains of rats with methylazoxy-methanol-induced microencephaly." Neurosci.Res.14. 13-25 (1992)

[文献書誌] Yoneda,Y.,Suzuki,T.,Ogita,K.,Han,D.: "Support for rakiolabaeling of a glycine recognition domain on the N-methyl-D-aspartate receptor ionophore complex by [ ^3H]5,7-dichlorokynurenate in rat brain." J.Neurochem.60. 634-645 (1993)

[文献書誌] Araki,T.,Tohyama,M.: "Region-specific expression of GABA_A receptor α_3 and α_4 subunits mRNAs in the rat brain" Mole.Brain Res.,. 12. 293-314 (1992)

[文献書誌] Araki,T.,Kiyama,H.,Tohyama,M.: "The GABA_A receptor γ_1 subunit is expressed by distinct neuronal populations" Mole.Brain Res.15. 121-132 (1992)

[文献書誌] Zhang,J.H.,Sato,M.,Tohyama,M.: "Co-expression of the α_1 and β_2 subunit genes of the GABA_A reaceptor in the magnocellular preoptic nucleus" Mole.Brain Res.15. 171-173 (1992)

[文献書誌] Hirouchi,M.,Hashimoto,T.: "Alteration in expression of GABA_A receptor alphal-subunit nRNA in following continuous ethanol administration" Europ.J.Pharmacol.(1993)

[文献書誌] Mizutani,M.,Hashimoto,T.fNakayasu,H.,Kuriyama,K.: "Alterations in cerebral GABA_B receptor binding during the formation of alcohol dependence." Pharmacology Communications. (1993)

[文献書誌] Hirouchi,H.,Ohkuma,S.,Kuriyama,K.: "Muscimol-induced reduction of GABA_A reaceptor alpha_1-subunit mRNA in in primary cultured neurons" Mole.Brain Res. 15. 327-331 (1992)

[文献書誌] Nakata,Y.,Takamatsu,H.,Kuroyanagi,N.,Nishio.H.,Segawa,T.,Akizawa;,T.: "Isolation of substance P binding protein from rat brain" J.Pharmacol.59. 313-319 (1992)

[文献書誌] Ogo,H.,Kuroyanagi,N.,Nishio,H.,Hirai,Y.,Akiyama,M.,Nakata,Y.: "Characterization of funtional substance P recepjtors in human astrocytoma cell line" J.Pharmacol.(suppl.). 61. 68 (1993)

[文献書誌] Yamawaki,Y.,m Ogawa,N.: "Successful treatment of levodopa-inducednefuroleptic malignant syndrome(NMS)and disseminated intravascular coagulation(DIC)in a patient with Parkinson'disease" Internal Medicine. 31. 1298-1302 (1992)

[文献書誌] Asanuma,M.,Wgawa,N.,Hirata,H.,Chou,H.,Kondo,Y.,Mori,A.: "Ischemia-induced changes in α-tubulin and β-actin mRNA in the gerbil brain and effects of bifemelane hydrochrolide" Brain Res.600. 243-248 (1993)

[文献書誌] 小川 紀雄,森 昭胤: "パーキンソン病とフリーラジカル" 神経精神薬理. 14. 735-744 (1993)

[文献書誌] Kito,S.,Miyoshi,R.: "Neurotransmitter Receptors:Neuroreceptor Mechanism in Brain" Plenum Press, 495 (1991)

1992 年度実績報告書

鬼頭昭三放送大学, 教養学部, 教授 (00010140)

[文献書誌] 野村靖幸: "記憶の細胞分子薬理" BIOmedica. 7(7). 708-713 (1992)

[文献書誌] 小川紀雄,森昭胤: "パーキンソン病とフリーラジカル" 神経精神薬理. 14. 735-744 (1993)