Neuropharmacological studies on the roles of glial receptors for neurotransmitters in gliosis

神经胶质受体在神经胶质增生中神经递质作用的神经药理学研究

• 批准号: 05454149
• 负责人: BABA Akemichi
• 金额: $ 4.03万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454149/
• 关键词: Gliosis; Astrocyte; Glutamic acid; Endothelins; Prostaglandins; Na, K-ATPase; IGF-I; Brain injury; 脳傷害; Na,K‐ATPase; IGF‐I; IGF-1

It is considered that glial cells have a role in brain injury, but exact mechanism is not known. In this project, the studies on receptors (glutamate, endothelins and prostaglandins) , glutamate transporter and Na^+, K^+-ATPase were carried out, in order to clarify the physiological and pathological roles of glial cells in brain. The following results were obtained.1. In cultured rat astrocytes, glutamate caused swelling and taurine release. The swelling was mediated via ionotropic glutamate receptors and glutamate transporters.2. Inhibitors of glutamate transporter interacts with metabotropic glutamate receptors in astrocytes.3. Endothelins caused a morphological change in cultured astrocytes. Our studies demonstrate that the peptides modulate cytoskeletal protein organization via a small G protein.4. Endothelin in vivo increased the number of GFAP-positive cells in rat brain.5. Structure and expression of prostaglandin F2a and thromboxane A2 receptors were clarified in astrocytes.6. IGF-I caused a isoform-specific induction of Na^+, K^+-ATPase in cultured astrocytes. The induction may be involved in the mitogenic action of the peptide on astrocytes.

人们认为胶质细胞在脑损伤中发挥作用，但确切机制尚不清楚。本课题从神经胶质细胞的受体（谷氨酸、内皮素和肾上腺素）、谷氨酸转运体和Na^+，K^+-ATP酶三个方面进行研究，以阐明神经胶质细胞在脑内的生理和病理作用。得到以下结果.在培养的大鼠星形胶质细胞，谷氨酸引起肿胀和牛磺酸的释放。肿胀是通过离子型谷氨酸受体和谷氨酸转运体介导的.谷氨酸转运体抑制剂与星形胶质细胞中代谢型谷氨酸受体相互作用.内皮素引起培养的星形胶质细胞的形态学变化。我们的研究表明，这些肽通过小G蛋白调节细胞骨架蛋白的组织.体内内皮素可增加大鼠脑内GFAP阳性细胞的数量.阐明了星形胶质细胞中前列腺素F2 a和血栓素A2受体的结构和表达. IGF-I可诱导培养星形胶质细胞中Na^+，K^+-ATP酶的亚型特异性表达。这种诱导作用可能与肽对星形胶质细胞的促有丝分裂作用有关。

项目成果

Y.H.Seong: "Inhibitory effect of guiseng total saponins on glutamate-induced swelling of cultured astro cytes" Biol,Pharm,Bull.18. 1776-1778 (1995)

Y.H.Seong：“桂参总皂苷对谷氨酸诱导的培养星形细胞肿胀的抑制作用”Biol，Pharm，Bull.18。

A. Baba: "Inhibitory glutamate response on cyclic AMP formation in cultured astrocytes." Neurosci. Lett.149. 182-184 (1993)

A. Baba：“培养的星形胶质细胞中谷氨酸对环 AMP 形成的抑制反应。”

Y. Koyama: "L-Glutamate-stimulated taurine release from rat cerebral cultured astrocytes." J. Neurosci. Res.38. 75-80 (1993)

Y. Koyama：“L-谷氨酸刺激大鼠大脑培养的星形胶质细胞释放牛磺酸。”

J. Kitanaka: "Tunicamycin inhibits prostaglandin F_2α receptor mediated phosphoinositide hydrolysis in cultured rat astrocytes." Neurochem. Res.19. 1545-1550 (1994)

J. Kitanaka：“衣霉素抑制培养的大鼠星形胶质细胞中前列腺素 F_2α 受体介导的磷酸肌醇水解。”19. 1545-1550 (1994)

J.Kitanaka: "cDNA cloning of a thromboxane A_2 receptor from rat astrocytes." Biochim.Biophys.Acta. 1265 (2-3). 220-223 (1995)

J.Kitanaka：“大鼠星形胶质细胞血栓素 A_2 受体的 cDNA 克隆。”