Pharmacological studies investigating the mechanisms controlling the peptidergic neurotransmitter release.

药理学研究研究控制肽能神经递质释放的机制。

• 批准号: 09670093
• 负责人: NAKATA Yoshihiro
• 金额: $ 2.05万
• 依托单位: HIROSHIMA 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-09670093/
• 关键词: substance P; primary afferent neuron; cultured rat spinal dorsal root ganglion cell; substance P release; nerve growth factor; preprotachykinin mRNA; interleukin-1 beta; cyclooxygenase-2; PPTmRNA; 遊離

Substance P (SP) in a dorsal root ganglion (DRG) is involved in one of the mechanisms responsible for the transmission of noxious stimuli. To elucidate the mechanisms controlling the release of this peptidergic neurotransmitter, the effects of neurotrophins or interleukin-1beta (IL-1beta) on SP synthesis and release were examined in primary cultured rat DRG cells.Nerve growth factor (NGF) increased SP content and it's precursor, preprotachykinin (PPT) mRNA in the DRG cells. Another neurotrophins tested, brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) had no effects on the SP content. High concentration of KCl (30mM) or capsaicin evoked the SP release from the cultured rat DRG cells in a Ca^<2+> dependent manner. IL-1beta is one of the cytokines which are synthesized and released from immune cells and considered to be important mediators during inflammation and hyperalgesia. When recombinant mouse IL-1beta was added to the DRG cells in the presence of NGF, IL-1beta evoked the SP release after 3 hours and increased SP content and PPT mRNA after 7 days. The effect of IL-1beta on the SP release was Ca^<2+> dependent and significantly inhibited by a IL-1 receptor antagonist and cyclooxygenase inhibitors, aspirin, indomethacin, NS-398 or dexamethasone. Furthermore IL-1beta increased inducible cyclooxygenase (COX)-2 mRNA without any effects on constitutive COX-1 mRNA in the incubation of 1 hour.Thus, it is suggested that IL-1beta evoked the release of this nociceptive neuropeptide in the DRG cells via specific IL-1 receptors, the mechanisms of which might be involved in prostanoid systems. It could be responsible for the hyperalgesic action with reference to inflammatory pain in primary afferent neuron to spinal cord pathway.

背根神经节（DRG）中的物质P（SP）参与了负责有害刺激传播的一种机制。为了阐明控制该肽胶质神经递质释放的机制，在原代培养的大鼠DRG细胞中检查了神经营养蛋白或神经营养蛋白或白介素-1Beta（IL-1Beta）对SP合成和释放的作用。NERVERED DRG细胞中的SP含量（NGF）SP含量和IT的Protorsor，IT的前体，前固醇（ppt）（ppt）（ppt），ppt in ngf含量。另一种测试，脑源性神经营养因子（BDNF）或Neurotrophin-3（NT-3）的神经营养蛋白对SP含量没有影响。高浓度的KCl（30mm）或辣椒素以CA^<2+>依赖性方式从培养的大鼠DRG细胞中唤起SP释放。 IL-1BETA是从免疫细胞合成并释放的细胞因子之一，在炎症和痛觉过敏过程中被认为是重要的介质。当在NGF存在的情况下，将重组小鼠IL-1Beta添加到DRG细胞中时，IL-1Beta在3小时后唤起了SP释放，并在7天后增加了SP含量和PPT mRNA。 IL-1BETA对SP释放的影响取决于IL-1受体拮抗剂和环氧酶抑制剂，阿司匹林，吲哚美辛，NS-398或地塞米松。此外，IL-1BetA增加了可诱导的环氧合酶（COX）-2 mRNA，对本育孵育1小时而对组成型COX-1 mRNA没有任何影响。因此，建议IL-1Beta唤起了该DRG细胞中通过特定的IL-1受体的DRG细胞中的DRG细胞中释放IL-1受体的释放。它可能是导致脊髓途径初级传入神经元炎症性疼痛的高温作用。

项目成果

A Inoue et al.: "Effects of neurotrophins or interleukin-1 beta on substance P synthesis in cultured rat dorsal root ganglia" Neurochemical Research. 24(1). 153 (1999)

A Inoue 等人：“神经营养素或白细胞介素 1β 对培养大鼠背根神经节 P 物质合成的影响”神经化学研究。

A Inoue et al.: "Effects of neurotrophins or interleukin-1β on substance P synthesis in cultured rat dorsal root ganglia" Neurochemical Research. 24(1). 153 (1999)

A Inoue 等人：“神经营养素或白细胞介素 1β 对培养大鼠背根神经节 P 物质合成的影响”《神经化学研究》24(1)。