预防主要会引起视网膜神经节细胞(+)镇痛新,一个σreceptor-1特定的配体。

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Dun Y, Thangaraju M,史密斯Prasad P, V Ganapathy,某人

预防主要会引起视网膜神经节细胞(+)镇痛新,一个σreceptor-1特定的配体。

角膜切削Vis Sci投资。2007年10月,48 (10):4785 - 94。

PubMed ID

17898305 (在PubMed

]

文摘

目的:σ(格)非阿片类受体,nonphencyclidine结合位点与健壮的神经保护属性。死亡之前,作者诱导RGC-5细胞系使用非常高的浓度(1毫米)兴奋性氨基酸谷氨酸(Glu)和同型半胱氨酸(Hcy)和证明了sigmaR1配体(+)镇痛新((+)-PTZ)可以防止细胞死亡。本研究的目的是建立一个生理相关范式进行测试的神经保护效应(+)-PTZ视网膜神经节细胞(RGCs)。方法:主要神经节细胞(GCs)被孤立immunopanning已经视网膜的老鼠,维护文化3天,和暴露于10、20、25日或50 microM Glu或10,25、50或100 microM Hcy 6到18个小时的存在与否(+)-PTZ (0.5, 1,3 microM)。细胞生存能力是衡量使用可行性和细胞凋亡原位检测荧光素化验。表达sigmaR1被免疫细胞化学评估,rt - pcr和免疫印迹。形态学的住神经节细胞,随着时间的推移他们的流程检查(0、3、6,18小时)后由微分干涉对比显微镜(DIC)接触excitotoxins (+) -PTZ的存在与否。结果:主要GCs显示强劲sigmaR1表达式。细胞敏感Glu或Hcy毒性(治疗长达25或50 microM Glu或50或100 microM Hcy诱导细胞死亡)。主要GCs预处理为1小时(+)-PTZ随后18 cotreatment 25 microM Glu和(+)-PTZ显示明显减少细胞死亡:25 microM Glu,仅50%; 25 microM Glu/0.5 microM (+)-PTZ, 38%; 25 microM Glu/1 microM (+)-PTZ, 20%; 25 microM Glu/3 microM (+)-PTZ, 18%. Similar results were obtained with Hcy. sigmaR1 mRNA and protein levels did not change in the presence of the excitotoxins. DIC examination of cells exposed to excitotoxins revealed substantial disruption of neuronal processes; cotreatment with (+)-PTZ revealed marked preservation of these processes. The stereoselective effect of (+)-PTZ for sigmaR1 was established in experiments in which (-)-PTZ, the levo-isomer form of pentazocine, had no neuroprotective effect on excitotoxin-induced ganglion cell death. CONCLUSIONS: Primary GCs express sigmaR1; their marked sensitivity to Glu and Hcy toxicity mimics the sensitivity observed in vivo, making them a highly relevant model for testing neuroprotection. Pretreatment of cells with 1 to 3 microM (+)-PTZ, but not (-)-PTZ, affords significant protection against Glu- and Hcy-induced cell death. sigmaR1 ligands may be useful therapeutic agents in retinal diseases in which ganglion cells die.

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药物靶点

药物	目标	类	生物	药理作用	行动
镇痛新	σ为靶标细胞内受体1	蛋白质	人类	是的	受体激动剂	细节