Analysis of functions of platelet-activating factor (PAF) in nervous system

血小板活化因子（PAF）在神经系统中的功能分析

• 批准号: 13670134
• 负责人: ISHII Satoshi
• 金额: $ 2.5万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670134/
• 关键词: platelet-activating factor; PAF; Receptor; Multiple sclerosis; Nociception; Neurotransmitter release; Knock-out mouse; Experimental Allergic Encephalomyelitis; Paired-pulse facilitation; posttetanic potentiation; 海馬; CA1; spontaneous miniature

1. Role for PAF receptor in multiple sclerosisExperimental allergic encephalomyelitis, an animal model of multiple sclerosis, was evoked in mice. PAF receptor-deficient (PAFR-KO) mice exhibited significantly reduced clinical scores when compared with wild-type (WT) mice, although the ratio of affected mouse and day of onset were not different between two groups. These data suggest an important role of PAF in the pathogenesis of EAE.2. Role for PAF receptor in nociceptionPAFR-KO mice displayed significantly reduced pain responses than WT mice, when the mouse hind paws received noxious thermal and chemical stimuli. The expression of PAF receptor mRNA was detected by RT-PCR in dorsal root ganglion neurons, which are primary afferents for transmission of nociceptive information from limbs. In addition, the calcium response was observed in the in vitro culture of dorsal root ganglion neurons in response to PAF. These data suggest that PAF potentiates pain sensation, at least, by modulating primary afferent neurons.3. Role for PAF receptor in neurotransmitter releaseUsing the mouse hippocampal slices, neurotransmitter release at Schaffer collateral-CA1 synapses was examined by two electrophysiological experiments : paired-pulse facilitation and posttetanic potentiation. The resulting data demonstrated that the two presynaptic phenomena were suppressed in PAFR-KO mice. Posttetanic potentiation was also suppressed in WT mice that were pretreated with WEB2086, a PAF antagonist. Together, these data suggest that PAF facilitates presynaptic neurotransmitter release.

1. PAF受体在多发性硬化中的作用在小鼠中诱发实验性变态反应性脑脊髓炎，一种多发性硬化的动物模型。与野生型（WT）小鼠相比，PAF受体缺陷型（PAFR-KO）小鼠的临床评分显著降低，尽管两组间受影响小鼠的比例和发病日期无差异。提示PAF在EAE的发病中起重要作用. PAF受体在伤害性感受中的作用PAFR-KO小鼠在后爪受到伤害性热刺激和化学刺激时，疼痛反应比WT小鼠显著降低。采用RT-PCR方法检测大鼠背根节神经元中PAF受体mRNA的表达。此外，在体外培养的背根神经节神经元中观察到PAF引起的钙反应。这些数据表明PAF至少通过调节初级传入神经元来增强痛觉。PAF受体在神经递质释放中的作用采用小鼠海马脑片，通过双脉冲易化和强直后增强两种电生理实验，研究了Schaffer侧支-CA 1突触的神经递质释放。所得数据表明，这两种突触前现象在PAFR-KO小鼠中受到抑制。用PAF拮抗剂WEB2086预处理的WT小鼠的强直后增强也受到抑制。总之，这些数据表明PAF促进突触前神经递质的释放。

项目成果

Klein, A., Pinho, V., Alessandrini, A.L., Shimizu, T., Ishii, S., Teixeira, M.M.: "Platelet-activating factor drives eotaxin production in an allergic pleurisy in mice"Brit. J. Pharmacol.. 135. 1213-1218 (2002)

Klein, A.、Pinho, V.、Alessandrini, A.L.、Shimizu, T.、Ishii, S.、Teixeira, M.M.：“血小板激活因子驱动小鼠过敏性胸膜炎中嗜酸细胞趋化因子的产生”Brit。

Klein, A., Pinho, V., Alessandrini, A.L., Shimizu, T., Ishii, S. and Teixeira, M.M.: "Platelet-activating factor drives eotaxin production in an allergic pleurisy in mice"Brit. J. Pharmacol.. 135. 1213-1218 (2002)

Klein, A.、Pinho, V.、Alessandrini, A.L.、Shimizu, T.、Ishii, S. 和 Teixeira, M.M.：“血小板激活因子驱动小鼠过敏性胸膜炎中嗜酸细胞趋化因子的产生”Brit。

Nagase, T., Uozumi, N., Aoki-Nagase, T., Terawaki, K., Ishii, S., Tomita, T., Yamamoto, H., Hashizume, K., Ouchi, Y, and Shimizu, T.: "A potent inhibitor of cytosolic phospholipase A_2, arachidonyl trifluoromethyl ketone, attenuates LPS-induced lung injur

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Klein A. et al.: "Platelet-activating factor drives eotaxin production in an allergic pleurisy in mice"Br. J. Pharmacol. 135. 1213-1218 (2002)

Klein A. 等人：“血小板激活因子驱动小鼠过敏性胸膜炎中嗜酸细胞趋化因子的产生”Br。

Nagase T, Uozumi N, Ishii S, Kita Y, Yamamoto H, Ohga E, Ouchi Y, Shimizu T.: "A pivotal role of cytosolic phospholipase A_2 in bleomycin-induced pulmonary fibrosis"Nature Med. 8. 480-484 (2002)

Nagase T、Uozumi N、Ishii S、Kita Y、Yamamoto H、Ohga E、Ouchi Y、Shimizu T.：“胞质磷脂酶 A_2 在博来霉素诱导的肺纤维化中的关键作用”Nature Med。