Cystic fibrosis and beta-adrenergic response of airway epithelial cell cultures.
Confluent cell sheets were cultured from the tracheal epithelium of normal humans or from tracheal and nasal epithelia of patients with cystic fibrosis (CF). Changes in short-circuit current (Isc) or cyclic AMP (cAMP) levels in response to 10(-5) M isoproterenol were measured. In CF tracheal cells the response to isoproterenol was transient, and the maximal increase in Isc was one-tenth normal. In CF nasal cells, isoproterenol or epinephrine caused only small transient increases in Isc. However, in both CF nasal and tracheal cells, the Ca ionophore, A23187, caused relatively large increases in Isc that were inhibited by the Cl transport blocker, bumetanide, suggesting that Cl secretion can be induced by raising intracellular levels of Ca. In normal tracheal cell sheets, cAMP levels increased within 15 s of isoproterenol addition and continued to increase for up to 20 min. Resting levels of cAMP in CF tracheal cells were not statistically different from those of normal cells and showed linear increases for up to 4 min after addition of isoproterenol. Changes in cAMP in CF nasal cells were similar to the changes in CF tracheal cells. After 2 min, all three cell types showed cAMP levels elevated approximately equal to 10-fold. These results suggest that receptor-activated stimulation of adenylate cyclase is normal in CF. However, though raised cAMP levels stimulate Cl secretion in normal, they are unable to do so in CF airway epithelial cells.
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D009298:Nasal Polyps / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014132:Trachea / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol