The pulmonary airways are the site of the most serious manifestation of cystic fibrosis. Airway plugging and infection proceed to bronchiectasis and loss of gas exchange function. Ion transport by airway epithelia from CF patients is abnormal in at least three ways: 1. cell chloride permeability is reduced 2. net sodium absorption is larger 3. sodium absorption is increased further by agents which induce chloride secretion in normal tissues. These defects in chloride and sodium transport may contribute to the pathophysiology of lung disease in CF by limiting the capacity to hydrate airway mucus. Neither the basis of these abnormal ion flows nor their interrelationship is known, but it does not appear that reduced cell chloride permeability, per se, should lead to increased sodium absorption. Instead, there seems to be a defect in the path of sodium absorption in CF airway epithelia. The proposed studies are designed to explore the increased basal sodium absorption and its further stimulation by beta adrenergic agents in CF tissues. The hypothesis that sodium entry is abnormally raised will be addressed by measuring sodium entry and sodium entry sites in CF and appropriate non-CF control airway epithelia cells. The hypothesis that basal Na+ K+ pump activity is raised and is further increased by beta adrenergic agents will be tested by measuring ouabain sensitive 86Rb uptake and sodium pump sites in CF and non-CF airway epithelial cells. The dependence of both entry and exit on cellular metabolism will be explored.
| Stutts, M J; Gatzy, J T; Boucher, R C (1988) Effects of metabolic inhibition on ion transport by dog bronchial epithelium. J Appl Physiol 64:253-8 |
| Stutts, M J; Gatzy, J T; Boucher, R C (1988) Activation of chloride conductance induced by potassium in tracheal epithelium. Pflugers Arch 411:252-8 |
| Stutts, M J; Knowles, M R; Gatzy, J T et al. (1986) Oxygen consumption and ouabain binding sites in cystic fibrosis nasal epithelium. Pediatr Res 20:1316-20 |
