1989 Fiscal Year Annual Research Report

運動系における情報伝達

Research Project

Project/Area Number	01623001
Research Institution	Nagoya University
Principal Investigator	永津俊治名古屋大学, 医学部, 教授 (40064802)
Co-Investigator(Kenkyū-buntansha)	川島紘一郎共立薬科大学, 薬学部, 教授 (50001037) 日高弘義名古屋大学, 医学部, 教授 (80100171) 永津郁子藤田学園保健衛生大学, 医学部, 教授 (80084573) 矢内原昇静岡県立大学, 薬学部, 教授 (80046250) 黒沢良和藤田学園保健衛生大学, 医学部, 教授 (10109259)
Keywords	パーキンソン病 / 情報伝達 / ドパミン / チロシン水酸化酵素 / 遺伝子cDNA / フェニルエタノールアミン / アセチルコリン / カルモデュリン
Research Abstract	運動系における情報伝達は、ドパミンなどのアミン系伝達物質、ガンマアミノ酪酸のようなアミノ酸系伝達物質、多種の神経ペプチドによって制御されている。シナプス前部神経伝達物質とシナプス後部の情報受容変換機構の分子レベルより解明を続けた。パーキンソン病の分子生物学は、ドーパミンを中心とするカテコールアミンの合成酵素、特にチロシン水酸化酵素の遺伝子、MPTP様神経毒の探索と、その合成酵素と代謝酵素の遺伝子、の2方向より進んでいる。チロシン水酸化酵素、ドーパ脱炭酸酵素、ドーパミンβ-水酸化酵素、フェニールエタノールアミンN-メチル基転移酵素のすべてのヒトのカテコールアミン生合成酵素のcDNA、遺伝子DNAのクローニングに成功(永津、黒沢)、ヒトチロシン水酸化酵素関連ペプチドの化学合成(矢内原)、ヒト芳香族L-アミノ酸脱炭酸酵素cDNAのクローニングと塩基配列の決定(黒沢、永津)、パーキソン病に対するlevodopa過量投与の過酸化反応促進作用(小川)、中枢コリン作動性神経におけるアセチルコリン生合成機構の検討(川島)、細胞内のCa^<2+>の受容蛋白で細胞内の情報伝達系の最重要因子カルモデュリン結合81k蛋白質の発見(日高)、線条体と黒質におけるPKC各サイズタイプの局在と機能(田中)、運動制御系のシナプス伝達機序を明かにするために脳シナプス前膜のイオンチャンネルの存在の研究(渡辺)、胎生後期から生後にかけて一過性に出現するチロシン水酸化酵素・免疫陽性細胞を、マウスの前嗅核領域と、大脳皮質に発見(永津郁)、新生児期一側大脳皮質障害後の大脳皮質脊髄路の再構成(島田)、一側脳基底核に病変を持つ症例の終夜睡眠ポリグラフの研究(瀬川)、MPTP投与マウスにおけるパーキンソン病の発症機構と免疫系の研究(永津)以上の生理病理における運動系関連伝達物質の新しい知見は、パーキンソン病などの運動系疾患の情報伝達の異常の分子機構解明に重要な手がかりを与えた。

Research Products

(43 results)

All Other

All Publications (43 results)

[Publications] Ichinose H.: "Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase." Biochem.Biophys.Res.Commun.164. 1024-1030 (1989)
[Publications] Nagatsu T.: "The human tyrosine hydroxylase gene." Mol.Cell.Neurobiol.9. 313-321 (1989)
[Publications] Ishii A.: "Ferrous ion activates the less active form of human adrenal tyrosine hydroxylase." Neurochem.Int.16. 59-64 (1990)
[Publications] Kobayashi k.: "Human dopamine β-hydroxylase gene:two mRNA typing having different 3'-terminl a regions are produced through alternative polyadenylation." Nucleic Acids.Res.17. 1089-1102 (1989)
[Publications] Uchida K.: "Synthesis of L-3,4-dihydroxyphenylallanine by tyrosine hydroxylase cDNA-transfected C6 cells:application for intracerebral grafting." J.Neurochem.53. 728-732 (1989)
[Publications] Sasaoka T.: "Structures of human phenylethanolamine N-methyltransferase gene:existence of two types of mRNA with different transcription initiation sites." Neurochem.Int.15. 555-565 (1989)
[Publications] Yanaihara N.: "Recent advances in brain-gut hormones." Arch.Histol.Cytol.52(Suppl.). 49-54 (1989)
[Publications] Zhang T.: "Gonadotropin-releasing hormone-associated peptide in rat brain tissues." Biomed.Res.10. 371-375 (1989)
[Publications] Zhang T.: "Distribution and molecular forms of pro-LHRH-related peptide immunoreactivity in porcine brain." Biomed.Res.10. 377-384 (1989)
[Publications] Okamura H.: "Immunocytochemistry of aormatic L-amino acid decarboxylase in the rat preoptic area and anterior hypothalamus,with special reference to tyrosine hydroxyasle immunoyctochemistry." Biogenic Amines.(1990)
[Publications] Tashiro Y.: "Tyrosine hydroxylase-like immunoreactive neurons in the striatum of the rat." Neurosci.Lett.97. 6-10 (1989)
[Publications] Yamada K.: "Immunocytochemical localization of amines and peptides in adrenal chromaffin cells of the house shrew(Suncus murinus)." Biogenic amines.(1990)
[Publications] J.C.Abougou.: "Phosphorylation of Caldesmon." FEBS Lett.(1989)
[Publications] Tokumitsu H.: "KN-62(1-[No-bis-5-isoquinolinesulfonyl]-N-methyl-Ltyrosyl-4-phenylpiperazine)specific inhibitor of Ca2+ calmodulin-dependent kinase II." J.Biol.Chem.(1989)
[Publications] Chijiwa T.: "Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by newly synthesized slective inhibitors of cyclic dependent protein kinase,H-89,in PC12D pheochromocytoma cells." J.Biol.Chem.(1989)
[Publications] J.C.Abougou.: "Phosphorylation of Caldesmon." FEBS Lett.(1989)
[Publications] Tokumitsu H.: "KN-62(1-[No-bis-5-isoquinolinesulfonyl]-N-methyl-Ltyrosyl-4-phenylpiperazine)specific inhibitor of Ca2+ calmodulin-dependent kinase II." J.Biol.Chem.(1989)
[Publications] Chijiwa T.: "Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by newly synthesized slective inhibitors of cyclic dependent protein kinase,H-89,in PC12D pheochromocytoma cells." J.Biol.Chem.(1989)
[Publications] Suzuki T.: "Hemicholinium-3-resistant choline uptake system linked to acetylcholine synthesis in the rat hippocampus." Neurosci.Lett.105. 211-214 (1989)
[Publications] Hanada N.: "Combined effects of acyclovir and human interferon-α on herpes simplex virus replication." J.Med.Virology.29. 7-12 (1989)
[Publications] Furune S.: "Transplacental effects of 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine(MPTP)on brain dopaminergic neurons in the mouse.An immunohistochemical study." Acta.Neuropath.79. 279-258 (1989)
[Publications] Oya Y.: "Uptake of N-methyle-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)and N-methyl-4-phenyl pyridinium ion(MPTP)into fetal mouse brain through the placenta." Neuroscience Lett.105. 221-226 (1989)
[Publications] Sato H.: "Biochemical and pharmacological characterization of somatostatin receptors in rat brain." Res.Commun.Chem.Pathol.Pharmacol.(1989)
[Publications] Ogawa N.: "Parkinsonism induced by indeloxazine hydrochloride." Clin.Therapeutics.(1989)
[Publications] Ogawa N.: "Neurotransmitter and receptor alterations in rat persistent dyskinesia model induced by iminodipropionitrile." Eur.Neurol.(1989)
[Publications] Iwane S.: "Golgi study on the homozygote(Ml/Ml)of macular mutant mouse." Brain Development.11. 154-160 (1989)
[Publications] Taga T.: "Restricion fragment length polymorphisms on the q24-q28 region of X chromosome among Japanese population." Jpn.J.Human Genet.34. 123-128 (1989)
[Publications] Ono K.: "Reorganization of the corticospinal tract following neonatal unilateral cortical ablation in rats." Brain Development.12. (1990)
[Publications] Shuntoh H.: "Involvement of protein kinase C in the Ca2+-dependent vesicular release of GABA from central and enteric neurons of the guinea pig." Brain Res.483. 384-388 (1989)
[Publications] Kuno T.: "Activationof type I cyclic AMP-dependent protein kinases is impaired by a point mutation in cyclic AMP binding sites." Eur.J.Pharmacol.172. 263-271 (1989)
[Publications] Ito A.: "The complete primary structure of calcineurin A,a calmodulin binding protein homologous with protein phospatases 1 and 2A." Biochem.Biophys.Res.Commun.163. 1492-1497 (1989)
[Publications] Suzuki T.: "In vivo experimental approach for determination of the central cholinergic neuronal activity.In:Alzheimers and Parkinson's Diseases." Nagatsu T.,Fisher A.and Yoshida M.eds.Plenum Press, (1989)
[Publications] Nagatsu,T.: "Abnormalcatecholamine metabolism in spontaneously hypertensiverats volammetry in vivo.In:Progress in hypertension,vol.1," H.Saito(Ed.).VNU Science Press,Utrecht,1-8 (1989)
[Publications] Nagatsu,T.: "Inhibitors and stimulatorsnof monoamine-synthesizing enzymes from microbes.In:Horizons on Antibiotic Research," B.D.Davis et al.(Eds.).Japan Antibiotics Research Association,Tokyo,121-137 (1989)
[Publications] Nagatsu,T.: "Physiological and clinical chemistry of biopterin.In:Medical Research Reviews," G.deStevens(Ed.).John Wiley & Sons,New York,25-44 (1989)
[Publications] Nagatsu,T.: "Molecular genetic approaches to the study of human catecholamine-synthesizing enzymes.In:Bioinformatics," O.Hatase,J.H.Wang(Eds.).Elsevier Science Publishers B.V.,Amsterdam,281-288 (1989)
[Publications] Kojima,K.: "Microbore HPLC for biological samples:catecholamines,peptides and proteins.In:PROGRESS IN HPLC,Vol.4," M.Yoshioka,S.Parvez,H.Parvez.(Eds.).VNU Science Press,Utrecht,211-227 (1989)
[Publications] Nagatsu,T.: "Roles of calcium ion in the regulation of tyrosine hydroxylase.In:Calcium protein signaling," H.Hidaka,E.Carafoli,A.R.Means and T.Tanaka(Eds.)Plenum Publishing Corporation,New York,425-433 (1989)
[Publications] Nakajima,T.: "Neuron-specific enolase and aromatic L-amino acid decarboxylase;neuroendocrine makers in immunohistochemistry.In:Endocrine pathology update," J.Lechago and T.Kameya(Eds.).Neuroendocrine Markers,Field and Wood,Inc.,Philadelphia,277-292 (1989)
[Publications] Segawa M.: "Rapid eye movements during stage REM are modulatedby nigrostriatal dopamine(NS-DA)neurons? In:“Basal Ganglia III."" G.Bernardi,ed.Pleneum Press., (1989)
[Publications] Segawa M.: "Long-term effects of L-Dopa on hereditary progressive dystonia with marked diurnal fluctuation.In:A.Berardelli,“Motor Disturbance II"." (1989)
[Publications] Segawa M.: "Pathophysiology of human locomotion-studies on human cases.Proceedings of the Vth TMIN international symposium on neurobiological basis of humanlocomotion." (1989)
[Publications] Nagatsu T.: "Regulation of catecholamine synthesis by tetrahydrobiopterin as cofactor of tyrosine hydroxylase.In:Progress in Catecholamine Research," A.Dahlstrom,R.H.Belmaker and M.sandler(Eds.)Alanb R.Liss,Inc.,New York,41-46 (1989)

1989 Fiscal Year Annual Research Report

運動系における情報伝達

Principal Investigator

永津 俊治 名古屋大学, 医学部, 教授 (40064802)

Research Products

[Publications] Ichinose H.: "Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase." Biochem.Biophys.Res.Commun.164. 1024-1030 (1989)

[Publications] Nagatsu T.: "The human tyrosine hydroxylase gene." Mol.Cell.Neurobiol.9. 313-321 (1989)

[Publications] Ishii A.: "Ferrous ion activates the less active form of human adrenal tyrosine hydroxylase." Neurochem.Int.16. 59-64 (1990)

[Publications] Kobayashi k.: "Human dopamine β-hydroxylase gene:two mRNA typing having different 3'-terminl a regions are produced through alternative polyadenylation." Nucleic Acids.Res.17. 1089-1102 (1989)

[Publications] Uchida K.: "Synthesis of L-3,4-dihydroxyphenylallanine by tyrosine hydroxylase cDNA-transfected C6 cells:application for intracerebral grafting." J.Neurochem.53. 728-732 (1989)

[Publications] Sasaoka T.: "Structures of human phenylethanolamine N-methyltransferase gene:existence of two types of mRNA with different transcription initiation sites." Neurochem.Int.15. 555-565 (1989)

[Publications] Yanaihara N.: "Recent advances in brain-gut hormones." Arch.Histol.Cytol.52(Suppl.). 49-54 (1989)

[Publications] Zhang T.: "Gonadotropin-releasing hormone-associated peptide in rat brain tissues." Biomed.Res.10. 371-375 (1989)

[Publications] Zhang T.: "Distribution and molecular forms of pro-LHRH-related peptide immunoreactivity in porcine brain." Biomed.Res.10. 377-384 (1989)

[Publications] Okamura H.: "Immunocytochemistry of aormatic L-amino acid decarboxylase in the rat preoptic area and anterior hypothalamus,with special reference to tyrosine hydroxyasle immunoyctochemistry." Biogenic Amines.(1990)

[Publications] Tashiro Y.: "Tyrosine hydroxylase-like immunoreactive neurons in the striatum of the rat." Neurosci.Lett.97. 6-10 (1989)

[Publications] Yamada K.: "Immunocytochemical localization of amines and peptides in adrenal chromaffin cells of the house shrew(Suncus murinus)." Biogenic amines.(1990)

[Publications] J.C.Abougou.: "Phosphorylation of Caldesmon." FEBS Lett.(1989)

[Publications] Tokumitsu H.: "KN-62(1-[No-bis-5-isoquinolinesulfonyl]-N-methyl-Ltyrosyl-4-phenylpiperazine)specific inhibitor of Ca2+ calmodulin-dependent kinase II." J.Biol.Chem.(1989)

[Publications] Chijiwa T.: "Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by newly synthesized slective inhibitors of cyclic dependent protein kinase,H-89,in PC12D pheochromocytoma cells." J.Biol.Chem.(1989)

[Publications] J.C.Abougou.: "Phosphorylation of Caldesmon." FEBS Lett.(1989)

[Publications] Tokumitsu H.: "KN-62(1-[No-bis-5-isoquinolinesulfonyl]-N-methyl-Ltyrosyl-4-phenylpiperazine)specific inhibitor of Ca2+ calmodulin-dependent kinase II." J.Biol.Chem.(1989)

[Publications] Chijiwa T.: "Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by newly synthesized slective inhibitors of cyclic dependent protein kinase,H-89,in PC12D pheochromocytoma cells." J.Biol.Chem.(1989)

[Publications] Suzuki T.: "Hemicholinium-3-resistant choline uptake system linked to acetylcholine synthesis in the rat hippocampus." Neurosci.Lett.105. 211-214 (1989)

[Publications] Hanada N.: "Combined effects of acyclovir and human interferon-α on herpes simplex virus replication." J.Med.Virology.29. 7-12 (1989)

[Publications] Furune S.: "Transplacental effects of 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine(MPTP)on brain dopaminergic neurons in the mouse.An immunohistochemical study." Acta.Neuropath.79. 279-258 (1989)

[Publications] Oya Y.: "Uptake of N-methyle-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)and N-methyl-4-phenyl pyridinium ion(MPTP)into fetal mouse brain through the placenta." Neuroscience Lett.105. 221-226 (1989)

[Publications] Sato H.: "Biochemical and pharmacological characterization of somatostatin receptors in rat brain." Res.Commun.Chem.Pathol.Pharmacol.(1989)

[Publications] Ogawa N.: "Parkinsonism induced by indeloxazine hydrochloride." Clin.Therapeutics.(1989)

[Publications] Ogawa N.: "Neurotransmitter and receptor alterations in rat persistent dyskinesia model induced by iminodipropionitrile." Eur.Neurol.(1989)

[Publications] Iwane S.: "Golgi study on the homozygote(Ml/Ml)of macular mutant mouse." Brain Development.11. 154-160 (1989)

[Publications] Taga T.: "Restricion fragment length polymorphisms on the q24-q28 region of X chromosome among Japanese population." Jpn.J.Human Genet.34. 123-128 (1989)

[Publications] Ono K.: "Reorganization of the corticospinal tract following neonatal unilateral cortical ablation in rats." Brain Development.12. (1990)

[Publications] Shuntoh H.: "Involvement of protein kinase C in the Ca2+-dependent vesicular release of GABA from central and enteric neurons of the guinea pig." Brain Res.483. 384-388 (1989)

[Publications] Kuno T.: "Activationof type I cyclic AMP-dependent protein kinases is impaired by a point mutation in cyclic AMP binding sites." Eur.J.Pharmacol.172. 263-271 (1989)

[Publications] Ito A.: "The complete primary structure of calcineurin A,a calmodulin binding protein homologous with protein phospatases 1 and 2A." Biochem.Biophys.Res.Commun.163. 1492-1497 (1989)

[Publications] Suzuki T.: "In vivo experimental approach for determination of the central cholinergic neuronal activity.In:Alzheimers and Parkinson's Diseases." Nagatsu T.,Fisher A.and Yoshida M.eds.Plenum Press, (1989)

[Publications] Nagatsu,T.: "Abnormalcatecholamine metabolism in spontaneously hypertensiverats volammetry in vivo.In:Progress in hypertension,vol.1," H.Saito(Ed.).VNU Science Press,Utrecht,1-8 (1989)

[Publications] Nagatsu,T.: "Inhibitors and stimulatorsnof monoamine-synthesizing enzymes from microbes.In:Horizons on Antibiotic Research," B.D.Davis et al.(Eds.).Japan Antibiotics Research Association,Tokyo,121-137 (1989)

[Publications] Nagatsu,T.: "Physiological and clinical chemistry of biopterin.In:Medical Research Reviews," G.deStevens(Ed.).John Wiley & Sons,New York,25-44 (1989)

[Publications] Nagatsu,T.: "Molecular genetic approaches to the study of human catecholamine-synthesizing enzymes.In:Bioinformatics," O.Hatase,J.H.Wang(Eds.).Elsevier Science Publishers B.V.,Amsterdam,281-288 (1989)

[Publications] Kojima,K.: "Microbore HPLC for biological samples:catecholamines,peptides and proteins.In:PROGRESS IN HPLC,Vol.4," M.Yoshioka,S.Parvez,H.Parvez.(Eds.).VNU Science Press,Utrecht,211-227 (1989)

[Publications] Nagatsu,T.: "Roles of calcium ion in the regulation of tyrosine hydroxylase.In:Calcium protein signaling," H.Hidaka,E.Carafoli,A.R.Means and T.Tanaka(Eds.)Plenum Publishing Corporation,New York,425-433 (1989)

[Publications] Nakajima,T.: "Neuron-specific enolase and aromatic L-amino acid decarboxylase;neuroendocrine makers in immunohistochemistry.In:Endocrine pathology update," J.Lechago and T.Kameya(Eds.).Neuroendocrine Markers,Field and Wood,Inc.,Philadelphia,277-292 (1989)

[Publications] Segawa M.: "Rapid eye movements during stage REM are modulatedby nigrostriatal dopamine(NS-DA)neurons? In:“Basal Ganglia III."" G.Bernardi,ed.Pleneum Press., (1989)

[Publications] Segawa M.: "Long-term effects of L-Dopa on hereditary progressive dystonia with marked diurnal fluctuation.In:A.Berardelli,“Motor Disturbance II"." (1989)

[Publications] Segawa M.: "Pathophysiology of human locomotion-studies on human cases.Proceedings of the Vth TMIN international symposium on neurobiological basis of humanlocomotion." (1989)

[Publications] Nagatsu T.: "Regulation of catecholamine synthesis by tetrahydrobiopterin as cofactor of tyrosine hydroxylase.In:Progress in Catecholamine Research," A.Dahlstrom,R.H.Belmaker and M.sandler(Eds.)Alanb R.Liss,Inc.,New York,41-46 (1989)

永津俊治名古屋大学, 医学部, 教授 (40064802)