摘要
The effects and the mechanisms of natural compounds ginkgolides on CFTR-mediate anion transport were investigated. The CFTR-mediate iodide influx rates were studied via a cell-based fluorescence assay done for FRT cells stably transfected by CFTR; transepithelial short-circuit current recordings of FRT cells and rat distal colon mucosa were respectively obtained. Cellular cAMP concentrations were measured via a radioimmunoassay analysis kit. Ginkgolide C dose-dependently increases CFTR-mediate anion transport, whereas ginkgolide A and B show no effect. The activation is sensitive to CFTR specific activator CFTRinh-172. Ginkgolide C stimulated amiloride and indomethacin pre-treated Cl currents in rat distal colon mucosa. Studies on FRT cells also manifest that ginkgolide C had additive effect with FSK/IBMX mixture and didn＇t elevate intracellular cAMP concentration, which implies it works through a direct binding mechanism. In conclusion, Ginkgolide C directly stimulates CFTR-mediate anion transport. Ginkgolide C may be a promising drug for the prevention and treatment of CFTR-related diseases such as idiopathic chronic pancreatitis（ICP）, habitual constipation, and kcratoconjunctivitis sicca（KCS）.
The effects and the mechanisms of natural compounds ginkgolides on CFTR-mediate anion transport were investigated. The CFTR-mediate iodide influx rates were studied via a cell-based fluorescence assay done for FRT cells stably transfected by CFTR; transepithelial short-circuit current recordings of FRT cells and rat distal colon mucosa were respectively obtained. Cellular cAMP concentrations were measured via a radioimmunoassay analysis kit. Ginkgolide C dose-dependently increases CFTR-mediate anion transport, whereas ginkgolide A and B show no effect. The activation is sensitive to CFTR specific activator CFTRinh-172. Ginkgolide C stimulated amiloride and indomethacin pre-treated Cl currents in rat distal colon mucosa. Studies on FRT cells also manifest that ginkgolide C had additive effect with FSK/IBMX mixture and didn＇t elevate intracellular cAMP concentration, which implies it works through a direct binding mechanism. In conclusion, Ginkgolide C directly stimulates CFTR-mediate anion transport. Ginkgolide C may be a promising drug for the prevention and treatment of CFTR-related diseases such as idiopathic chronic pancreatitis（ICP）, habitual constipation, and kcratoconjunctivitis sicca（KCS）.
基金
Supported by Changchun Municipal Science and Technology Fund(No.2008116)
Science and Technology Fund of Jilin Province(No.20090464)
