Role of Endogenous Glutaminergic Systems in Mammalian Pineal Gland : A novel inhibitory systems for melatonin synthesis.

内源性谷氨酰胺能系统在哺乳动物松果体中的作用：褪黑激素合成的新型抑制系统。

• 批准号: 09672233
• 负责人: MORIYAMA Yoshinori
• 金额: $ 1.86万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672233/
• 关键词: pinealocyte; serotonin; melatonin; acetylcholine; glutamate; synaptic vesicle; secretory grannle; receptor; 松果体; D-アスパラギン酸; SV2B; 概日リズム; ホルモン制御

Mammalian pinealocytes synthesize and secrete melatonin, a hydrophobic hormone that affects many physiological functions such as circadian rhythm and seasonal reproduction.Besides melatonin, pinealocytes have been found to secrete L-glutamate by exocytic mechanism : pinealocytes accumulate L-glutamate in microvesicles (MVs) and secrete it through Ca2+ regulated exocytosis.Previously we showed that this system functions as a negative regulatatory mechanism for melatonin synthesis.In this project, we characterized in somje details on the endogenous glutaminergic systems and obtained following results.(1) Metabotropic glutamate receptor type 3 (mGluR3) is involved in the systems through an inhibitory G proteins-mediated signaling cascade.(2) Acetylcholine triggers glutamate exocytosis via nicotinic acetylcholine receptor in rat pinealocytes.(3) MVs contain some synaptic vesicle marker proteins such as SV2B, confirming MVs as counterparts of neuronal synaptic vesicles.(4) Pinealocytes contain high concentration of D-aspartate, which may also function as an inhibitory transmitters.(5) GluR1, an isoform of AMPA-type iGluRs, is predominantly expressed and functions in pinealocytes.

哺乳动物松果体细胞合成并分泌褪黑激素，这是一种疏水性激素，影响昼夜节律和季节性生殖等许多生理功能。除了褪黑激素外，松果体细胞还被发现通过胞吐机制分泌L-谷氨酸：松果体细胞在微泡（MV）中积累L-谷氨酸并通过胞吐机制分泌L-谷氨酸。 Ca2+调节胞吐作用。之前我们表明该系统作为褪黑激素合成的负调节机制。在本项目中，我们详细描述了内源性谷氨酰胺能系统，并获得了以下结果。（1）代谢型谷氨酸受体3（mGluR3）通过抑制性G蛋白介导的信号参与该系统 (2) 乙酰胆碱通过大鼠松果体细胞中的烟碱乙酰胆碱受体触发谷氨酸胞吐作用。(3) MV 含有一些突触小泡标记蛋白，如 SV2B，证实 MV 是神经元突触小泡的对应物。(4) 松果体细胞含有高浓度的 D-天冬氨酸，其 (5) GluR1 是 AMPA 型 iGluR 的同种型，主要在松果体细胞中表达并发挥作用。

项目成果

S.Yatsushiro et al.: "L-Aspartate but not the D-form is secreted through microvesicle-mediated exocytosis and is sequestered through Na^+-dependent transporter in rat pinealocytes." J.Neurochem.69. 340-347 (1997)

S.Yatsushiro 等人：“L-天冬氨酸而非 D-形式是通过微泡介导的胞吐作用分泌的，并通过大鼠松果体细胞中 Na+ 依赖性转运蛋白进行隔离。”

Y.Moriyama,H.Yamada,M.Hayashi,T.Oda and A.Yamaguchi.: "4. Identification of D-aspartate in rat pheochromocytoma PC12 cells." Neurosci.Lett.248. 57-60 (1998)

Y.Moriyama、H.Yamada、M.Hayashi、T.Oda 和 A.Yamaguchi.：“4. 大鼠嗜铬细胞瘤 PC12 细胞中 D-天冬氨酸的鉴定。”

M.Hayashi, T.Oda, A.Yamaguchi.Y.Moriyama, and H.Yamada: "Identification of D-aspartate in rat pheochromocytoma PC12 cells." Neurosci.Lett.248. 57-60 (1998)

M.Hayashi、T.Oda、A.Yamaguchi.Y.Moriyama 和 H.Yamada：“大鼠嗜铬细胞瘤 PC12 细胞中 D-天冬氨酸的鉴定。”

H.Yamada, A.Ogura, S.Koizumi, A.Yamaguchi, and Y.Moriyama: "Acetylcholine triggers L-glutamate expcytosis via nicotinic receptor and inhibits melatonin synthesis in rat pinealocytes." J.Neurosci. 18. 4946-4952 (1998)

H.Yamada、A.Ogura、S.Koizumi、A.Yamaguchi 和 Y.Moriyama：“乙酰胆碱通过烟碱受体触发 L-谷氨酸胞吐作用，并抑制大鼠松果体细胞中褪黑激素的合成。”

S.Ishio, H.Yamada, M.Hayashi, S.Yatsushiro, T.Noumi, A.Yamaguchi and Y.Moriyama: "D-aspartate modulates melatonin synthesis in rat pinealocyte." Neurosci.Lett.249. 143-146 (1998)

S.Ishio、H.Yamada、M.Hayashi、S.Yatsushiro、T.Noumi、A.Yamaguchi 和 Y.Moriyama：“D-天冬氨酸调节大鼠松果体细胞中褪黑激素的合成。”