| Project/Area Number |
04304037
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | THE UNIVERSITY OF THE AIR |
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Principal Investigator |
KITO Shozo The University Div.of Professor of the Air, Health Sciences, 教養学部, 教授 (00010140)
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| Co-Investigator(Kenkyū-buntansha) |
TOHYAMA Masaya Osaka Univ., Dept.of Med., Professor, 医学部, 教授 (40028593)
FUJISAWA Hitoshi Asahikawa, Dept.of Medicine, Professor Medical College, 教授 (10027039)
KURIYAMA Kinya Kyoto Pre.Univ.of Medicine, Professor, 教授 (20079734)
SATO Masamichi Kyoto Univ., Dept.of Pharmacol., Professor, 薬学部, 教授 (80025709)
NOMURA Yasuyuki Hokkaido Univ., Dept. of Pharmacol., Professor, 薬学部, 教授 (00034041)
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| Project Period (FY) |
1992 – 1993
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| Keywords | long-term effects / protooncogenes / nicotine / long-term potentiation / GABA receptor / excitatory amino acids / substance P / kinase IV |
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| Research Abstract |
It has been known that cell stimulation by growth factors and hormones often causes changes of gene expression which lead to long-term effects of cell response.
Much attentions have been forcused on this kind of responses from viewpoints of basic and clinical pharmacology. The particularly important is that several kinds of protooncogenes are participated in chemical signal transduction as well as mechanism of drug addiction.
In this study, mechanisms of cell responses evoked by various neuroactive substances in the central nervous system were investigated from viewpoints of chemistry, molecular biology, electrophysiology and morphology and following results were obtained. (1) Nicotine inhibited dexamethasoneinduced kainic acid cytotoxcity dose-dependently. On the other hand, single injection of estrogen into rat caused cytoprotection of amygdala neurons at lower doses and cytotoxicity at higher doses. (2) By means of electrophsiologcal studies using hippocampal slices, it was found that
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cholinergic regulation is participated in long-term potentiation at mossy fiber-CA3 synapes. (3) Changes of intracellular GABA receptor structure due to alcoholic addiction was studied. As the results, alcoholic addiction caused changes of both GABA_A and GABA_B receptors. It was assumed that such disorders of suppressive function are connected to development of alcoholic abstinence. (4) Mechanism of long-term effects of excitatory amino acids in the brain was studied from viewpoints of gene transduction. (5) Expression of mRNA of gamma1 and gamma2 subunit of GABA_A receptors and AMPA type glutamic acid receptors, Glu R1, 2 were examined in the dorsal root ganglion neurons and spinal dorsal horn neurons. (6) To examine substance P's effect on the brain, mechanism of substance P receptor expression was examined using U-87 MG cells. (7) Effect of pentylentetrazole and kainic acid administration on various gene expression in the hippocampus was studied. (8) Expression of c-fos mRNA induced by cycolohexamide was inhibited by cenelifide. (9) Kinase IV was purfied from rat brain. This kinase was found to be a multifunctional protein kinase specifically distributed in the brain. Less
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