Abstract
beta-adrenergic stimulation of glycoprotein secretion was shown to be decreased in submandibular glands of Cystic Fibrosis (CF) mice. The defective response was partially restored by the methylxanthine, IBMX or cpt-cyclic AMP. Cholinergic stimulation of pancreatic amylase secretion was not affected in CF mice, demonstrating that this is not a generalised depression of protein secretion. The data are the first to show that the CF mouse mimics the protein secretion defect in CF human submandibular cells and that the mechanism of correction of the CF defect is via elevation of cyclic AMP. The results are therefore invaluable towards devising a rational pharmaceutical therapy for CF patients.
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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Adrenergic beta-Agonists / pharmacology*
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Amylases / metabolism
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Animals
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Carbachol / pharmacology*
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / metabolism
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Cyclic AMP / pharmacology
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Cystic Fibrosis / metabolism*
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Glucosamine / metabolism
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Glycoproteins / biosynthesis*
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Heterozygote
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Humans
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Male
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Mice
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Mice, Mutant Strains
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Pancreas / drug effects
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Pancreas / enzymology
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Submandibular Gland / drug effects
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Submandibular Gland / metabolism*
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Thionucleotides / pharmacology
Substances
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Adrenergic beta-Agonists
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Glycoproteins
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Thionucleotides
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8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
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Carbachol
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Cyclic AMP
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Amylases
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Glucosamine
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1-Methyl-3-isobutylxanthine