Altered Biochemical Regulation of Secretion in Cystic Fibrosis Epithelial Cells
A link between alteration in the protein coded for by the CF gene (Riordan et al., 1989) and the abnormal epithelial cell physiology in CF must be established in order to recognise potential site(s) of intervention to correct the secretory abnormality. Defective B-adrenergic responses are seen in all affected epithelial cells in CF (McPherson and Dormer, 1987, 1988). Thus, sweating was stimulated by isoproterenol in control but not in CF sweat glands (Sato and Sato, 1984). Secretion of mucins was increased in response to isoproterenol in control but not in CF submandibular acinar cells (McPherson et al., 1985, 1986). CF submandibular acinar cells also showed a much reduced secretion of amylase in response to isoproterenol and noradrenaline, both agonists acting via a B-adrenergic effect (McPherson et al., 1985, 1986). Cl- transport in cultured CF sweat duct cells (Pedersen, 1986) and airways epithelial cells (Welsh and Liedtke, 1986; Frizzell et al., 1986; Widdicombe et al., 1986; Cotton et al., 1987) was also shown to be defective in response to isoproterenol. In all of these epithelial cells cyclic AMP rise was shown to be normal in response to isoproterenol (McPherson and Dormer, 1987, 1988), indicating either that the defect is beyond the site of cyclic AMP formation, or that this measurement is not relevant to the function of isoproterenol in opening Cl- channels or stimulating protein secretion.
KeywordsCystic Fibrosis Submandibular Gland Airway Epithelial Cell Mucin Secretion Amylase Release
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