20(S)-原人参二醇促进CFTR氯离子通道开放  

Natural Compound 20(S)-Protopanaxadiol Activates Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel

作　　者：刘军[1] 那万里[2] 辛伟红[2] 刘丽丹[3] 于波[1] 麻彤辉[1] 杨红[1] 

机构地区：[1]东北师范大学膜通道研究实验室 [2]吉林大学中日联谊医院,长春130031 [3]吉林大学护理学院,长春130021

出　　处：《高等学校化学学报》2008年第4期731-735,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:30470405,30570864,30670477);吉林省杰出青年基金(批准号:20030112);教育部青年骨干教师奖励计划;留学回国人员科研基金资助

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.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 cellbased 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 AFS08 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, keratoconjunc- tivitis sicca and habitual constipation.

关 键 词：囊性纤维化 CFTR氯离子通道 突变 天然化合物 激活剂 

分 类 号：O657[理学—分析化学] Q73[理学—化学]