A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosistransmembrane conductance regulator protein

A selective cyclic nucleotide PDES inhibitor corrected the defective mucin secretion response to the beta-agonist isoproterenol in submandibular acina r cells inhibited by antibody directed against the cystic fibrosis transmem brane conductance regulator. The PDES inhibitor was as effective as cpt-cyc lic AMP or a selective PDE4 inhibitor. However, the PDES inhibitor had no e ffect on basal or isoproterenol-stimulated cyclic AMP levels and did not st imulate mucin secretion. The results showing, for the first time, correctio n of the CFTR mucin secretion defect by a PDES inhibitor, which may involve cyclic GMP, mill have a major impact in development of a rational drug tre atment for cystic fibrosis. (C) 1999 Federation of European Biochemical Soc ieties.