Activation of CFTR-mediated Cl- Transport by Capsaicinoids in Cell Culture Model

Previous studies reported that capsaicin potentiates Delta 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 Delta 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) pmol/L and (150.2 +/- 7.4) mu mol/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.