| 抗抑郁新化合物SIPI-C和SIPI-F对PC12细胞内游离钙离子浓度的影响 |
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| 引用本文： | 周慧,汪溪洁,翁志洁,李建其,马璟.抗抑郁新化合物SIPI-C和SIPI-F对PC12细胞内游离钙离子浓度的影响[J].中国药理学与毒理学杂志,2013,27(2):145-149. |
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| 作者姓名： | 周慧 汪溪洁 翁志洁 李建其 马璟 |
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| 作者单位： | 1. 上海医药工业研究院国家上海新药安全评价研究中心, 上海 201203;;2. 上海医药工业研究院 化学制药新技术中心, 上海 200040 |
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| 摘 要： | 目的研究抗抑郁新化合物SIPI-C和SIPI-F对PC12细胞内游离钙离子浓度(Ca2+]i)的影响,初步探讨其神经毒性的机制。方法 接种PC12细胞于经胶原Ⅰ包被的培养皿,加入钙离子荧光探针Fluo-3/AM染色后,用激光共聚焦显微镜分别记录①有钙外液中,10μmo.lL-1的SIPI-A,B,C和F对PC12细胞Ca2+]i的影响;②有钙外液中,1,10和100μmol.L-1的SIPI-C和SIPI-F对Ca2+]i的影响;③有钙外液中,硝苯地平10μmo.lL-1对10μmo.lL-1的SIPI-C或SIPI-F作用的影响;④无钙细胞外液中,10μmo.lL-1SIPI-C和SIPI-F对Ca2+]i的影响。结果 有钙外液中,SIPI-A 10μmol.L-1给药后Ca2+]i下降,10μmol.L-1的SIPI-B,SIPI-C和SIPI-F分别使Ca2+]i增加27%(P<0.05),84%(P<0.05)和87%(P<0.01);SIPI-C和SIPI-F明显升高Ca2+]i;同时给予SIPI-C 10μmol.L-1和硝苯地平10μmo.lL-1或SIPI-F 10μmo.l L-1和硝苯地平10μmo.lL-1,给药后荧光强度立即上升达到峰值,随后下降,Ca2+]i分别增加24%和15%(P<0.05)。在无钙外液中,SIPI-C和SIPI-F 10μmo.lL-1分别使Ca2+]i增加16%和18%(P<0.01)。结论 抗抑郁化合物SIPI-C和SIPI-F可以引起PC12细胞中Ca2+]i显著增加,此影响可能与其神经毒性有关。
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| 关 键 词： | 抗抑郁药物 烷醇哌嗪衍生物 SIPI-C SIPI-F PC12细胞 细胞内钙离子浓度 |
| 收稿时间： | 2012-3-31 |
| 修稿时间： | 2012-9-6 |
Effect of new antidepressants SIPI-C and SIPI-F on cytosolic free Ca2+ concentration in PC12 cells |
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| ZHOU Hui, WANG Xi-jie, WENG Zhi-jie, LI Jian-qi, MA Jing.Effect of new antidepressants SIPI-C and SIPI-F on cytosolic free Ca2+ concentration in PC12 cells[J].Chinese Journal of Pharmacology and Toxicology,2013,27(2):145-149. |
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| Authors: | ZHOU Hui WANG Xi-jie WENG Zhi-jie LI Jian-qi MA Jing |
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| Institution: | 1. National Shanghai Center for New Drug Safety Evaluation & Research, Shanghai Institute of Pharmaceutical Industry, Shanghai 201203, China;2. Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China |
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| Abstract: | OBJECTIVE To investigate the effect of SIPI-C and SIPI-F on cytosolic free Ca2+ concentration (Ca2+]i) in PC12 cells. METHODS PC12 cells were cultured in culture dish coated with collagenⅠ. After incubation at 37℃ for 40-50 min in 10 μmol·L-1 Fluo-3/AM enriched media, the Ca2+]i changes were continuously measured by the confocal laser scanning microscope: 1 effect of SIPI-A, B, C and F 10 μmol·L-1 on Ca2+]i in normal extracellular fluid; 2 effect of SIPI-C and SIPI-F 1, 10 and 100 μmol·L-1 on Ca2+]i in normal extracellular fluid; 3 effect of nifedipine 10 μmol·L-1 on effects of SIPI-C or SIPI-F 10 μmol·L-1 in normal extracellular fluid; 4 effect of 10 μmol·L-1 SIPI-C or SIPI-F on Ca2+]i in non-calcium extracellular fluid. RESULTS SIPI-A 10 μmol·L-1 decreased Ca2+]i while SIPI-B, SIPI-C and SIPI-F 10 μmol·L-1 resulted in the elevation of intracellular calcium by 27%, 84% and 87% in normal extracellular fluid. In SIPI-C or SIPI-F 10 μmol·L-1 combined with nifedipine 10 μmol·L-1 group, Ca2+]i was elevated by 24% and 15% after application of compounds. At the same concentration, SIPI-C and SIPI-F resulted in the elevation of Ca2+]i by 16% and 18% in non-calcium extracellular fluid. CONCLUSION SIPI-C and SIPI-F increase Ca2+]i which could be related to SIPI-C and SIPI-F induced neurotoxicity. |
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| Keywords: | antidepressive drugs aryl alkanol piperazine derivatives SIPI-C SIPI-F PC12 cells cytosolic Ca2+ concentration |
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