【摘 要】
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Calcium-activated chloride channels(CaCCs) are the crucial regulators of transepithelial fluid secretion, smooth muscle contraction and sensory transduction. Re
【机 构】
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Membrane Channel Research Laboratory,School of Life Sciences
论文部分内容阅读
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 TMEM 16A(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 identi- fied 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.
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