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

作　　者：HAO Feng YI Fei ZHANG Di N1NG Yan SU Wei-heng FENG Xue-chao YANG Hong MA Tong-hui 

机构地区：[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

出　　处：《Chemical Research in Chinese Universities》2011年第3期461-463,共3页高等学校化学研究（英文版）

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

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 influx assay in Fischer rat thyroid epithelial cells to coexpress ANO1 and an iodide-sensitive fluorescent 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.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 influx assay in Fischer rat thyroid epithelial cells to coexpress ANO1 and an iodide-sensitive fluorescent 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） 

分 类 号：Q424[生物学—神经生物学] S567[生物学—生理学]