Effects of Autonomic Agents and Chemical Mediators on Ion Transport by Canine Tracheal Epithelium

Active ion transport by the airway epithelium plays an important role in maintaining the effective defense mechanisms of theairway by regulating the volume and composition of the airway fluid. We investigated the abilities of adrenergic agents, cholinergic agents, and chemical mediators to modulate ion transport in canine tracheal epithelium, using Ussing-type chambers. Transepithelial electric potential difference (PD), resistance (R), and short circuit current (SCC) of the tracheal epithelium were measured before and during exposure to a drug or after a change in the perfusate composition. The mean values and S.E. (N=41) of PD, R, and SCC during the control period were -18±4mV (luminal negative to submucosa), 240±42Ω•cm2, and 50±5μA/cm2, respectively. Ouabain (10-4M), an inhibitor of Na+-K+-ATPase, in the mucosal bath abolished PD and SCC. Replacement of luminal Na by choline reversibly reduced PD and SCC. These findings suggest that PD and SCC of the tracheal epithelium are maintained by the transcellular transport of luminal Na toward the mucosa. Isoproterenol (10-5M), epinephrine (10-4M), and norepinephrine (10-4M) markedly increased both PD and SCC. Acetylcholine (10-4M) and histamine (10-4M) did not alter SCC significantly. Prostaglandin E1 (10-6M) and F2α (10-5M) slightly increased PD and SCC. These results indicate that adrenergic and cholinergic agents induce different patterns of effect on ion transport (adrenergic-dominant) in the tracheal epithelium. Thus, the effects of autonomic agents and chemical mediators on ion transport may explain, in part, the pathogenesis of airway disorders observed in many respiratory diseases.