Activation of CFTR-mediated Cl^- Transport by Magnolin  

作　　者：JIN Ling-ling LIU Xin SUN Yan LIN Sen ZHOU Na XU Li-na YU Bo HOU Shu-guang YANG Hong 

机构地区：[1]Liaoning Province Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University,Dalian 116029, P. R. China [2]China-Japan Union Hospital, Jilin University, Changchun 130033,P R. China [3]Qianwei Affiliate Hospital, Jilin University, Changchun 130021, P. R. China

出　　处：《Chemical Research in Chinese Universities》2008年第2期187-191,共5页高等学校化学研究（英文版）

基　　金：Supported by the National Natural Science Foundation of China(Nos30470405 and 30570864)

摘　　要：Magnolin is a herbal compound from Magnolia biondii Pamp. It possesses numerous biological activities. Cystic fibrosis transmembrane conductance regulator（CFTR） is an epithelial chloride channel that plays a key role in the fluid secretion of various exocrine organs. In the present study, the activation of CFTR-mediated chloride transport by magnolin is indentified and characterized. In CFTR stably transfected FRT cells, magnolin increases CFTR CI- currents in a concentration-dependent manner. The activation of magnolin on CFTR is rapid, reversible, and cAMP-dependent. Magnolin does not elevate cellular cAMP level, indicating that it activates CFTR by direct binding and interaction with CFTR protein. Magnolin selectively activates wildtype CFTR rather than mutant CFTR. Magnolin may present a novel class of therapeutic lead compound tbr the treatment of diseases associated with reduced CFTR function such as keratoconjunctivitis sicca, idiopathic chronic pancreatiti, and chronic constipation.Magnolin is a herbal compound from Magnolia biondii Pamp. It possesses numerous biological activities. Cystic fibrosis transmembrane conductance regulator（CFTR） is an epithelial chloride channel that plays a key role in the fluid secretion of various exocrine organs. In the present study, the activation of CFTR-mediated chloride transport by magnolin is indentified and characterized. In CFTR stably transfected FRT cells, magnolin increases CFTR CI- currents in a concentration-dependent manner. The activation of magnolin on CFTR is rapid, reversible, and cAMP-dependent. Magnolin does not elevate cellular cAMP level, indicating that it activates CFTR by direct binding and interaction with CFTR protein. Magnolin selectively activates wildtype CFTR rather than mutant CFTR. Magnolin may present a novel class of therapeutic lead compound tbr the treatment of diseases associated with reduced CFTR function such as keratoconjunctivitis sicca, idiopathic chronic pancreatiti, and chronic constipation.

关 键 词：Cystic fibrosis CFTR MUTATION Magnolin ACTIVATOR 

分 类 号：R730[医药卫生—肿瘤]