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Previous studies reported that capsaicin potentiates F508 mutant cystic fibrosis transmembrane conductance regulator(CFTR) channel gating defect by transfected cell-based assays. It has been postulated that orally ingested capsaicin may conceptually be used to develop a therapeutic strategy to treat gastrointestinal disorders in CF patients. We tried to reproduce and extend those pre-clinical data of previous studies. Cell-based fluorescence functional measurements in Fischer thyroid epithelial cells(FRT) expressing CFTR showed no effect of capsaicin on potentiating F508-CFTR, while genistein showed a strongly positive activity. Studies show that capsaicin and dihydrocapsaicin activated cAMP-prestimulated wild-type CFTR in a dose-dependent manner with a maximal response of 70% of that activated by genistein, thus gave an apparent EC50 of (40.4±6.8) μmol/L and (150.2±7.4) μmol/L respectively. Preliminary study shows that the binding sites for capsaicin and dihydrocapsaicin may be probably partially overlapped with that for genistein because the maximal activation of wild-type CFTR with genistein is partially blocked by capsaicin and dihydrocapsaicin.
Previous studies reported that capsaicin potentiates F508 mutant cystic fibrosis transmembrane conductance regulator(CFTR) channel gating defect by transfected cell-based assays. It has been postulated that orally ingested capsaicin may conceptually be used to develop a therapeutic strategy to treat gastrointestinal disorders in CF patients . We tried to reproduce and extend those pre-clinical data of the following studies. Cell-based fluorescence functional measurements in Fischer thyroid epithelial cells (FRT) expressing CFTR showed no effect of capsaicin on potentiating F508-CFTR, while genistein showed a strongly positive activity . Studies show that capsaicin and dihydrocapsaicin activated cAMP-prestimulated wild-type CFTR in a dose-dependent manner with a maximal response of 70% of that activated by genistein, which gave a clear EC50 of (40.4±6.8) μmol/L and ( 150.2±7.4) μmol/L respectively. Preliminary study shows that the binding sites for capsaicin and dihydrocapsaicin may be pr Obably partially overlapped with that for genistein because the maximal activation of wild-type CFTR with genistein is partially blocked by capsaicin and dihydrocapsaicin.