Abstract
A selective cyclic nucleotide PDE5 inhibitor corrected the defective mucin secretion response to the beta-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
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Animals
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Antibodies / pharmacology
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Cyclic AMP / metabolism
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Cyclic GMP / metabolism
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Cyclic Nucleotide Phosphodiesterases, Type 5
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Cystic Fibrosis Transmembrane Conductance Regulator / immunology*
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Cystic Fibrosis Transmembrane Conductance Regulator / physiology
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Humans
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Isoproterenol / pharmacology
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Mucins / drug effects
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Mucins / metabolism*
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Purinones / pharmacology
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Pyridazines / pharmacology
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Pyridines / pharmacology
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Rats
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Rolipram / pharmacology
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Submandibular Gland / drug effects
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Submandibular Gland / metabolism*
Substances
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Antibodies
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CFTR protein, human
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Mucins
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Purinones
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Pyridazines
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Pyridines
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SK&F 95654
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2-(2-propoxyphenyl)-6-purinone
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Cystic Fibrosis Transmembrane Conductance Regulator
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Cyclic AMP
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3',5'-Cyclic-GMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 5
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PDE5A protein, human
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Pde5a protein, rat
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Cyclic GMP
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Rolipram
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Isoproterenol
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1-Methyl-3-isobutylxanthine