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

FEBS Letters

Pereira, Malcolm M.C.²  Dormer, Robert L.²  Murray, Kenneth J.¹  Lloyd Mills, Chris²  McPherson, Margaret A.² 

[1] SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (North), Third Avenue, Harlow, Essex CM19 5AW, UK;Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK

关键词: Cystic fibrosis transmembrane conductance regulator protein;    Submandibular;    Mucin secretion;    Cyclic nucleotide PDE inhibitor;    CF;    cystic fibrosis;    CFTR;    cystic fibrosis transmembrane conductance regulator protein;    cpt-cyclic AMP;    8-(4-chlorophenylthio)-cyclic AMP;    IBMX;    3-isobutyl-1-methylxanthine;    KHB;    Krebs–Henseleit bicarbonate;    KLH;    keyhole limpet haemocyanin;    NBD;    nucleotide-binding domain;    PDE;    cyclic nucleotide phosphodiesterase;   

DOI  :  10.1016/S0014-5793(99)01672-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A selective cyclic nucleotide PDE5 inhibitor corrected the defective mucin secretion response to the β-agonist isoproterenol in submandibular acinar cells inhibited by antibody directed against the cystic fibrosis transmembrane conductance regulator. The PDE5 inhibitor was as effective as cpt-cyclic AMP or a selective PDE4 inhibitor. However, the PDE5 inhibitor had no effect on basal or isoproterenol-stimulated cyclic AMP levels and did not stimulate mucin secretion. The results showing, for the first time, correction of the CFTR mucin secretion defect by a PDE5 inhibitor, which may involve cyclic GMP, will have a major impact in development of a rational drug treatment for cystic fibrosis.

【 授权许可】

Unknown