FEBS Letters | |
A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein | |
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
【 预 览 】
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