【摘要】 利用氯离子通道细胞荧光测定模型对386种中药单体化合物进行筛选,发现20(S)-原人参二醇对依赖于cAMP的CFTR氯离子通道具有激活作用.20(S)-原人参二醇能够以剂量依赖的方式激活野生型CFTR氯离子通道,其激活作用通过更为可靠的氯离子通道短路电流测定系统得到证实.20(S)-原人参二醇对CFTR氯离子通道的激活效应具有作用迅速且可逆的特点.其在发挥激活作用时依赖于腺苷环化酶激动剂Forskolin的存在,单独与细胞孵育不提高细胞内cAMP的水平,表明对CFTR氯离子通道的激活作用是通过与CFTR直接结合实现的.该化合物对ΔF508-CFTR突变氯离子通道的开放也具有特征相似的激活作用.更多还原

【Abstract】 In the present study,we identified a natural compound 20(S)-protopanaxadiol as an effective CFTR chloride channel activator by screening of 386 single compounds from Chinese medicinal herbs by cell-based fluorescent assay.The CFTR-stimulating activity was confirmed by an Ussing chamber short-circuit current assay.The activation is rapid,reversible and cAMP-dependent.The compound does not elevate cellular cAMP level,implying that it worked in a direct binding way.20(S)-Protopanaxadiol can also restore the impaired chloride conductance of ΔF508 mutant CFTR.In our study a new natural compound was identified that may be useful for probing CFTR channel gating mechanisms and as a leading compound to develop pharmacological therapy of CFTR-related disease such as cystic fibrosis,idiopathic chronic pancreatitis,keratoconjunctivitis sicca and habitual constipation.更多还原