药学学报, 2013, 48(6): 848-854
引用本文:
杨 爽, 于 波, 张耀方, 王 雪, 杨 红. 川陈皮素对囊性纤维化跨膜传导调节因子的激活作用[J]. 药学学报, 2013, 48(6): 848-854.
YANG Shuang, YU Bo, ZHANG Yao-fang, WANG Xue, YANG Hong. The activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator chloride channel[J]. Acta Pharmaceutica Sinica, 2013, 48(6): 848-854.

川陈皮素对囊性纤维化跨膜传导调节因子的激活作用
杨 爽, 于 波, 张耀方, 王 雪, 杨 红*
(辽宁师范大学生命科学学院, 辽宁省生物技术与分子药物研发重点实验室, 辽宁 大连 116033)
摘要:

本实验利用荧光淬灭实验和膜片钳技术在稳定表达人CFTR和荧光绿蛋白突变体EYFP/H148QFischer大鼠甲状腺上皮细胞 (Fischer rat thyroid, FRT) , 测定川陈皮素 (nobiletin) 对囊性纤维化跨膜传导因子 (cystic fibrosis transmembrane conductance regulator, CFTR) 氯离子通道的激活作用。结果发现, 川陈皮素以剂量依赖的方式激活CFTR氯离子通道的Cl 转运活性, 且这种活性是快速、可逆的, 并能够被CFTR特异性抑制剂CFTRinh-172完全抑制。初步的分子机制研究表明, 川陈皮素是以与CFTR直接作用来激活通道活性的。进一步的研究结果显示, 川陈皮素能够有效刺激小鼠气管黏膜下腺液体分泌速度。因此, 川陈皮素可能发展成为治疗包括支气管扩张在内的CFTR相关疾病的先导药物。

关键词:   
The activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator chloride channel
Abstract:

Aim of the present study is to investigate activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity.  CFTR-mediated iodide influx assay and patch-clamp tests were done on FRT cells stably co-transfected with human CFTR and EYFP/H148Q.  Nobiletin potently activated CFTR chloride channel activity in a dose- and time-dependent manner.  The CFTR blocker CFTRinh-172 could completely reverse the effect.  Preliminary mechanism study indicated that nobiletin activated CFTR chloride channel through a direct binding way.  In addition, ex vivo tests done on mice trachea showed that nobiletin time-dependently stimulated submucosal gland fluid secretion.  Nobiletin may be a therapeutic lead compound in treating CFTR-related diseases including disseminated bronchiectasis.

Key words:   
收稿日期:
相关功能
PDF(1780KB) Free
打印本文
0
作者相关文章