Cystic fibrosis (CF) is the most common recessively inherited lethal or semilethal disease affecting primarily exocine glands. Based on the recent observations that CF sweat glands fail to show beta adrenergic sweat secretion in vivo and in vitro and that the CF sweat duct has a higher (than control) luminal negative potential, we propose: 1, to further elucidate the nature and mechanism of beta adrenergic sweat secretion in normal and its dysfunction in CF sweat glands; 2, to examine whether isolated CF secretory cells fail to accumulate cAMP in response to various cAMP enhancing agonists; 3, to characterize the electrophysiological response of CF secretory cells to beta adrenergic stimulation; 4, to elucidate the site and mechanisms of abnormal ionic (particularly C1-) permeability in the isolated perfused CF sweat duct; 5, to reexamine the effect of the CF factor, if any, on ductal Na absorption; and, 6, to elucidate whether CF sweat shows any protein electrophoresis patterns different from control. Methods include isolation of the CF sweat gland, induction sweating in vitro, preparation of dispersed cells, purification of secretory cells, microperfusion of duct, measurement of transepithelial and membrane protein, gel electrophoresis techniques, all of which are available in the PI's laboratory. New information to be derived from the proposed effort should deepen our understanding into the nature of the defect in the CF sweat gland, which may help guide us to new therapeutic approaches for patients with CF.
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