脳内生理活性物質の長期効果と情報伝達機構

1993 Fiscal Year Annual Research Report

• Project/Area Number: 04304037
• Research Institution: THE UNIVERSITY OF THE AIR
• Principal Investigator: 鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)
• Co-Investigator(Kenkyū-buntansha): 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)
• Keywords: 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

Research Abstract

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)。

Research Products

• [Publications] Kito,S.: "A cytoprotective effect of nicotine on hippocampal neurons." Society for Neuroscience Abstracts. 19. 772.15 (1993)
• [Publications] Miyoshi,R.: "Effect of nicotine on neurotransmitter release from the rat hippocampus." Society for Neuroscience Abstracts. 384.6 (1993)
• [Publications] Kito,S.: "Effect of glucocorticoid on hippocampal neurons:in vivo and in vitro studies." Neurochemical Research. 18. 801-860 (1993)
• [Publications] Tohda,C.K.: "Increase in neurite formation and acetylcholine release by transfection of growth-associated protein-43cDNA into NG108-15 cells." Joumal of Neurochemistry. 61. 526-532 (1993)
• [Publications] Nomura,Y.: "Inducible nitric oxide synthase in glial cells." Neuroscience Research. 18. 103-107 (1993)
• [Publications] Okano,K.: "Pharmacological evidence for involvement of:excitatory amino acids in:aversive responses induced by intrathecal substance P in rats." Biol.Pharm.Bull.16. 861-865 (1993)
• [Publications] Yabuuchi,K.: "In situ hybridization study of interleukin-1beta mRNA induced by kainic acid in the rat brain." Molecular Brain Research. 20. 153-161 (1993)
• [Publications] Minami,M.: "In situ hybridization study of kappa-opioid receptor mRNA in the rat brain." Neuroscience Letters. 162. 161-164 (1993)
• [Publications] Minami,M.: "Cloning and experssion ofa cDNA for the rat kappa-opioid receptor." FEBS Letters. 329. 291-295 (1993)
• [Publications] Nakamoto,H.: "Possible involvement of descending monoaminergic systems to spinal dorsal horn in antinociception by peroral(6)-shogaol in rats." Pain Research. 8. 93-98 (1993)
• [Publications] Matsuoka,N.: "Role of somatostatin in the augmentation of hippocampal long-term potentiation by FR121196,a putative cognitive enhancer." European Joumal of Pharmacology. 241. 27-34 (1993)
• [Publications] Maeda,T.: "Bidirectional modulation of long-term potentiation by carbachol via M_1and M_2muscarinic receptors in guinea pig hippocampal mossy fiber-CA3 synapses." Brain Research. 619. 324-330 (1993)
• [Publications] Ozaki,M.: "A vaccinia virus vector for efficiently introducing into hippocampal slices." Biochemical and Biophysical Research Communications. 193. 653-660 (1993)
• [Publications] Nakamura,S.: "Potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor function by a nootropic drug,.idebenone." Biol Pharm.Bull.17. 70-73 (1994)
• [Publications] Hirouchi,M.: "Alteation of GABA_Areceptor alpha_1-subunit mRNA in mouse brain following continuous ethanol inhalation." European Journal of Pharmacology-Molecular! Pharmacology Section. 247. 127-130 (1993)
• [Publications] Mizutani,H.: "Alterations in cerebral GABA_Breceptor binding during the formation of alchol dependence." Pharmacology Communications. 3. 139-146 (1993)
• [Publications] Enomoto,R.: "Differential potentiation by spermidine of abilities of a variety of displacers for 〔^3H〕MK-801 binding in hippocampal synaptic membranes." Neurosceince Research. 16. 217-224 (1993)
• [Publications] Pingping,Z.: "Comparative studies on binding of 3 different ligands to the N-methyl-D-aspartate recognition domain in brain synaptic membranes treated with triton X-100." Brain Research. 609. 253-261 (1993)
• [Publications] Yoneda,Y.: "Excitatory amino acid receptor binding in hippocampus of gerbils with transient global brain ischemia." Brain Research. 613. 21-31 (1993)
• [Publications] Yoneda,Y.: "Support for radiolabeling of a glycine recognition domain on the N-methyl-D-aspartate receptor ionophore complesx by 5,7-〔^3H〕dichlorokynurenate in rat brain." Journal of Neurochemistry. 60. 634-645 (1993)
• [Publications] Suzuki,T.: "Potentiation by polyamines of an interaction of noncompetitive antagonists at the N-methyl-D-aspartate receptor ionophore complex with phosphatidylserin" Neurochem.Int.23. 427-440 (1993)
• [Publications] Yoneda,Y.: "Selectively high expression of the transcription factor AP1 in telencephalic structures of epileptic E1 mice." Neuroscience Letters. 161. 161-164 (1993)
• [Publications] Pingping,Z.: "Further evidence for multiple forms of an N-methyl-D-aspartate recognition domain in rat brain using membrane bindng techniques." Journal of Neurochemistry. 61. 1865-1873 (1993)
• [Publications] Sato,K.: "The differential expression patterns of messenger RNA_Sencoding non-N-methyl-D-aspartate glutamate receptor subunits(GluRl-4)in the rat brain." Neuroscience. 52. 515-539 (1993)
• [Publications] Fujita,M.: "Ontogeny of dopamine transporter mRNA expression in the rat brain." Molecular Brain Research. 19. 222-226 (1993)
• [Publications] Ogo,H.: "Modulation of substance preceptor in human astrocytoma cells by antisense oligodeoxynucleotides." General Pharmacology in press. (1994)
• [Publications] Miyoshi,R.: "Effect of caerulein on expression of the immediate-early genes c-fos and zif/268 in the rat brain." Neuroscience Letters. 145. 205-208 (1992)
• [Publications] Miyoshi,R.: "Effect of estrogen on immediate early gene expression in the rat brain." Society for Neuroscience Abstracts. 18. 57.1 (1992)
• [Publications] Asanuma,M.: "Ischemia-induced changes in alpha-tubulin and beta-actin mRNA in the gerbil brain and effects of bifemelane hydrochloride." Brain Research. 600. 243-248 (1993)
• [Publications] Hirata,H.: "Effect of chronic ceruletide treatment on dopaminergic neurotransmitters,receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile." Brain Research. 604. 197-204 (1993)
• [Publications] Ogawa,N.: "The preventive effect of cyclosporin A,an immunosuppressant,on the late onset reduction of muscarinic acetylcholone receptors in gerbil hippocampus after transient forebrain ischemia." Neuroscience Letters. 152. 173-176 (1993)
• [Publications] Chou,H.: "Rapid response of striatal muscarinic M_1-receptor mRNA to muscarinic cholinergic agents in rat brain." Molecular Brain Research. 19. 211-214 (1993)
• [Publications] Fujisawa,H.: "Ragulation of the activities of Ca^<2+>/calmodulin-dependent multifunctional protein kinases." Biomedical Research. 14. 99-102 (1993)
• [Publications] Okuno,S.: "Raquirement of brain extract for the activity of brain calmodulin-dependent protein kinase IV expressed in escherichia coli." J.Biochem.114. 167-170 (1993)
• [Publications] Kameshita,I.: "Autophosphorylation of calmodulin-dependent protein kinase IV from rat cerebral cortex." J.Biochem.113. 583-590 (1993)