Chemical Pathology of Receptors in Autopsied Brains of Patients with Schizophrenia

精神分裂症患者尸检大脑中受体的化学病理学

• 批准号: 62570489
• 负责人: MITA Tatsuo
• 金额: $ 1.02万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570489/
• 关键词: Human brain; Schizophrenia; Dopamine uptake; ^3H-GBR-12935 binding sites; Histamine receptor; ^3H-Mepyramine binding sites; フェンサイクリジン結合部位; 興奮性アミノ酸受容体; カルシウムチャネル; ニトレンジピン; Cキカーゼ; フォルボールエステル受容体; ドパミン取り込み; GBR-12935

We have investigated the alterations of dopamine uptake sites, histamine H_1 receptors and phencyclidine binding sites in the postmortem brain samples from patients with chronic schizophrenia, using [^3H]GBR-12935, [^3H]mepyramine and [^3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([^3H]TCP) as a respective radioligand.1. The binding sites for [^3H]GBR-12935, a selective dopamine uptake inhibitor, tended to increase in the putamen of patients with schizophrenia as compared with age-matched control subjects, although the difference between the means was not statistically significant.2. The binding sites for [^3H]mepyramine, a selective histamine H_1 receptor antagonist, were identified in the human brain, and they were significantly decreased by 35 % in the frontal cortex of patients with schizophrenia.3. The phencyclidine binding sites labeled by [^3H]TCP, which were considered to be coupled with N-methyl-D-aspartate (NMDA)-sensitive L-glutamate receptors, were shown to be influenced by L-glutamate, glycine and Mg^<2+> in the human brain, as demonstrated in other mammals. There were no significant chenges in the specific [^3H]TCP binding in the frontal cortex or hippocampus of patients with schizophrenia.

我们使用 [^3H]GBR-12935、[^3H]美吡拉明和 [^3H]1-[1-(2-噻吩基)环己基]哌啶研究了慢性精神分裂症患者死后脑样本中多巴胺摄取位点、组胺 H_1 受体和苯环己哌啶结合位点的变化 ([^3H]TCP) 作为各自的放射性配体。1。与年龄匹配的对照受试者相比，选择性多巴胺摄取抑制剂[^3H]GBR-12935的结合位点在精神分裂症患者的壳核中趋于增加，尽管平均值之间的差异不具有统计学意义。2．在人脑中发现了选择性组胺H_1受体拮抗剂[^3H]美吡拉明的结合位点，在精神分裂症患者的额叶皮质中，其结合位点显着减少了35%。 3．由[^3H]TCP标记的苯环己哌啶结合位点被认为与N-甲基-D-天冬氨酸(NMDA)敏感的L-谷氨酸受体偶联，显示出受到人脑中的L-谷氨酸、甘氨酸和Mg^2+的影响，正如在其他哺乳动物中所证实的那样。精神分裂症患者额叶皮层或海马中的特异性[^3H]TCP结合没有显着变化。

项目成果

白川治、中井隆、北村登、橋本健志、西野直樹、三田達雄/ヒト死後脳phencyclidine結合部位に対するL-グルタミン酸、グリシンおよびMg^<2+>の影響: "27" 神経化学, 248-249 (1988)

Osamu Shirakawa、Takashi Nakai、Noboru Kitamura、Kenji Hashimoto、Naoki Nishino、Tatsuo Mita/L-谷氨酸、甘氨酸和 Mg^<2+> 对人死后大脑中苯环己哌啶结合位点的影响：“27”神经化学，248-249（ 1988）

白川治: 第30回日本神経化学大会論文集. 26. 538-540 (1987)

Osamu Shirakawa：第 30 届日本神经化学会议论文集。26. 538-540 (1987)。

三田達雄: "続分裂病とは何か-分裂病脳における受容体" 東京大学出版会, 13 (1987)

三田龙夫：“什么是精神分裂症后遗症？精神分裂症大脑中的受体”东京大学出版社，13（1987）

Hirai, M.; Kitamura, N.; Hashimoto, T.; Nakai, T.; Mita, T.; Shirakawa, O.; Yamadori, T.; Amano, T.; Noguchi-Kuno, S.; Tanaka, C.: "[^3H]GBR-12935 binding sites in human striatal membranes: Binding characteristics and changes in Parkinsonians and schizoph

平井，M.；

白川治: 薬物・精神・行動. (1988)

白川修：毒品、思想和行为（1988）。