THE EFFECT OF BREFELDIN-A ON TERBUTALINE-INDUCED SODIUM-ABSORPTION INFETAL-RAT DISTAL LUNG EPITHELIUM

We studied the effect of brefeldin A, which inhibits the intracellular trafficking of membrane proteins from the cytosolic pool to the cell surface, on terbutaline (a beta(2)-specific adrenergic agonist)-induce d alterations in ion transport by primary monolayer cultures of fetal rat distal lung epithelium. The amiloride-sensitive short circuit curr ent (Isc) increased 2.5-fold 50 mill after application of terbutaline (10 mu M) from basolateral side; this response was abolished by pretre atment with brefeldin A (1 mu g/ml). Brefeldin A did not suppress the Na+/K+ pump capacity. Single channel patch clamp experiments demonstra ted that terbutaline increased the density of amiloride-sensitive Na+- permeable nonselective cation channels on the apical cell membrane and this action was blocked by brefeldin A. These observations suggest th at beta 2-specific adrenergic agonists promote the trafficking of amil oride sensitive Na+-permeable nonselective cation channels to the apic al cell surface.