The G551D-CFTR mutation causing cystic fibrosis(CF)results from a missense mutation at codon 551 (G551D)in the gene encoding of the cystic fibrosis transmembrane conductance regulator(CFTR). The G551D mutation in CFTR results in a reduced functionaI channeI but G551D-CFTR is appropriately inserted in the apicaI membrane. In previous studies we discovered a class of high-affinity bicyclooctane(BC0) G55 1D-CFTR activators(G55 1DBcos)with Kd down to 1mol/L. In this study, we analyzed the pharmaco-Iogical activation of G551D-CFTR by the G551DBcos by means of short circuit current analysis and cell-based fluorescence quenching assay. The G551DBcos-induced G551D-CFTR activation is cAM P-dependent and is Iess sensitive to thiazolidinone CFTR inhibitor CFTRinh-172. These data suggest that(1)the phosphoryla-tion of G551D-CFTR by protein kinase A is required for the activation by G55l[)Bcos；(2)G551DBcoS and CFTRinh-172 may act at the same site on the G551D-CFTR molecule.