Chemical Research in Chinese Universities ›› 2009, Vol. 25 ›› Issue (6): 887-890.

• Articles • Previous Articles     Next Articles

Direct Activation of CFTR Chloride Channel by Natural Compound Theophylline

LIU Xin1, GE Hong2, ZHAO Xue-liang1, HOU Ting-ting2, SUN Juan-juan2, YANG Jing-bo3, HE Cheng-yan1* and YANG Hong2   

  1. 1. China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China;
    2. School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029, P. R. China;
    3. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China
  • Received:2008-12-03 Revised:2009-02-06 Online:2009-11-25 Published:2010-01-25
  • Contact: HE Cheng-yan. E-mail: chengyanhe469@vip.sina.com
  • Supported by:

    Supported by the Program for New Century Excellent Talents in University of China(No.NCET-07-0406), the Program for  Excellent Talents in University of Liaoning Province, China(No.2006R33), Changchun Municipal Science and Technology Fund (No.2007sf19), and Project of General Administration of Quality Supervision of China(No.2006IK145).

Abstract:

Theophylline has been widely used in the treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentration. Because cystic fibrosis transmembrane conductance regulator(CFTR) is a cAMP-dependent Cl channel that plays key roles in fluid secretion in vivo, we postulated that theophylline activates CFTR channel gating. We found  (1) theophylline stimulated CFTR-mediated anion transport in a concentration-dependent manner, and CFTR specific blocker completely reversed the effect; (2) theophylline had no effect on ΔF508 or G551D mutant CFTR chloride channel activity; (3) theophylline had additive effect with forskolin(FSK) and 3-isobutyl-xanthin(IBMX), thus a direct binding activation mechanism was suggested. In conclusion, the results may provide a clue to elucidating the molecular mechanism of theophylline activities and theophylline may present a novel lead drug in treating CFTR-related disease.

Key words: Theophylline; Cystic fibrosis transmembrane conductance regulator; Activator