Natural compound nuciferine activates chloride channel of wild type and △F508 mutant cystic fibrosis transmembrane conductance regulator

Abstract

Abstract: AIM:To identify CFTR Cl^- channel gating potentiators from natural compounds. METHODS:A stably transfected Fischer thyroid epithelial (FRT) cell line co-expressing human CFTR and a green fluorescent protein mutant with ultra-high halide sensitivity (YFP-H148Q) was used to measure CFTR-mediated iodide influx rate stimulated by the 386 natural compounds. RESULTS:Nuciferine was identified as an effective activator of wild-type CFTR chloride channel by screening of 386 single compounds from Chinese medicinal herbs. The CFTR-stimulating activity is rapid and reversible. Nuciferine does not elevate cellular cAMP level and activates phophorylated CFTR, suggesting that it works by direct binding to CFTR molecule. Nuciferine can also potentiate the Cl^- transport of △F508 mutant CFTR. CONCLUSION:Nuciferine was identified as an effective CFTR chloride channel activator. Nuciferine may be useful for probing CFTR channel gating mechanisms and as a lead compound to develop pharmacological therapy of CFTR-related disease such as cystic fibrosis, idiopathic chronic pancreatiti, keratoconjunctivitis sicca and habitual constipation.

Key words: cystic fibrosis transmembrane conductance regulator, chloridion transport, nuciferine, potentiator

CLC Number:

R965.2

LIN Sen, HOU Shu-guang, JIN Ling-ling, YU Bo, YANG Hong. Natural compound nuciferine activates chloride channel of wild type and △F508 mutant cystic fibrosis transmembrane conductance regulator[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(2): 138-143.

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