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高等学校化学研究 ›› 2011, Vol. 27 ›› Issue (3): 461-463.

• Articles • 上一篇    下一篇

Identification of Herbal Compound Imperatorin with Adverse Effects on ANO1 and CFTR Chloride Channels

HAO Feng1, YI Fei1, ZHANG Di1, NING Yan1, SU Wei-heng1, FENG Xue-chao1, YANG Hong2 and MA Tong-hui1*   

  1. 1. Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, P. R. China;
    2. School of Life Sciences, Liaoning Normal University, Dalian 116029, P. R. China
  • 收稿日期:2010-12-06 修回日期:2011-01-19 出版日期:2011-05-25 发布日期:2011-04-29
  • 通讯作者: Tong-hui E-mail:math108@nenu.edu.cn
  • 基金资助:

    Supported by the National Natural Science Foundation of China(Nos.30670477, 30973577 and 30770493) and the National Basic Research Program of China(No.2009CB521908).

Identification of Herbal Compound Imperatorin with Adverse Effects on ANO1 and CFTR Chloride Channels

HAO Feng1, YI Fei1, ZHANG Di1, NING Yan1, SU Wei-heng1, FENG Xue-chao1, YANG Hong2 and MA Tong-hui1*   

  1. 1. Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, P. R. China;
    2. School of Life Sciences, Liaoning Normal University, Dalian 116029, P. R. China
  • Received:2010-12-06 Revised:2011-01-19 Online:2011-05-25 Published:2011-04-29
  • Contact: Tong-hui E-mail:math108@nenu.edu.cn
  • Supported by:

    Supported by the National Natural Science Foundation of China(Nos.30670477, 30973577 and 30770493) and the National Basic Research Program of China(No.2009CB521908).

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摘要： Calcium-activated chloride channels(CaCCs) are the crucial regulators of transepithelial fluid secretion, smooth muscle contraction and sensory transduction. Recently, compelling evidence has indicated that TMEM16A(ANO1 or anoctamin-1) is a bona fide calcium-acvtivated chloride channel. A few small molecule CaCCs regulators are available for functional and therapeutic studies. We screened 126 natural compounds from Chinese herbs. Screening was performed with an iodide in?ux assay in Fischer rat thyroid epithelial cells to coexpress ANO1 and an iodide-sensitive ?uorescent indicator(EYFP-H148Q/I152L). Imperatorin, a coumarin compound, was identified to inhibit ANO1-mediated chloride transport activated by multiple calcium-elevating agonists. The inhibitory  effect is dose-dependent with IC50 ~14.63 μmol/L. Interestingly, imperatorin activated CFTR chloride channel with EC50 ~35.52 μmol/L. The adverse effects of imperatorin on CaCC and CFTR chloride channels will make it useful in pharmacological dissection of chloride transport in airway and intestinal epithelium. Further studies are required to evaluate the therapeutic effects of imperatorin on hypertension, asthma and certain tumors.

关键词: Calcium-acvtivated chloride channel(CaCC), ANO1, Imperatorin, Cystic fibrosis transmembrane conductance regulator(CFTR)

Abstract: Calcium-activated chloride channels(CaCCs) are the crucial regulators of transepithelial fluid secretion, smooth muscle contraction and sensory transduction. Recently, compelling evidence has indicated that TMEM16A(ANO1 or anoctamin-1) is a bona fide calcium-acvtivated chloride channel. A few small molecule CaCCs regulators are available for functional and therapeutic studies. We screened 126 natural compounds from Chinese herbs. Screening was performed with an iodide in?ux assay in Fischer rat thyroid epithelial cells to coexpress ANO1 and an iodide-sensitive ?uorescent indicator(EYFP-H148Q/I152L). Imperatorin, a coumarin compound, was identified to inhibit ANO1-mediated chloride transport activated by multiple calcium-elevating agonists. The inhibitory  effect is dose-dependent with IC50 ~14.63 μmol/L. Interestingly, imperatorin activated CFTR chloride channel with EC50 ~35.52 μmol/L. The adverse effects of imperatorin on CaCC and CFTR chloride channels will make it useful in pharmacological dissection of chloride transport in airway and intestinal epithelium. Further studies are required to evaluate the therapeutic effects of imperatorin on hypertension, asthma and certain tumors.

Key words: Calcium-acvtivated chloride channel(CaCC), ANO1, Imperatorin, Cystic fibrosis transmembrane conductance regulator(CFTR)