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 cel...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）.展开更多
基金Supported by Changchun Municipal Science and Technology Fund(No.2008116)Science and Technology Fund of Jilin Province(No.20090464)
文摘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）.
