GLUCOCORTICOSTEROIDS INCREASE SODIUM-TRANSPORT IN MIDDLE-EAR EPITHELIUM

The effect of glucocorticosteroids on ion transport was investigated o n a middle ear cell line with the short-circuit current (I-sc) techniq ue. Dexamethasone (DXM) produced a dose- and time-dependent increase i n I-sc. Concentration of half-maximal stimulation was 2.68 x 10(-8) M. This effect was blunted by the glucocorticoid antagonist RU-38486 and was related to Na+ transport, as evidenced by the inhibition induced by 1) apical addition of the Na+ channel inhibitor benzamil (10(-6) M) or 2) substitution of Na+ with N-methylglucamine in the incubation me dium. The increase in Na+ transport resulted from a primary modulation of apical Na+ entry, since 1) the Na+-K+-ATPase activity of cellular homogenates was not modified by corticosteroids and 2) the DXM-induced increase in the ouabain-sensitive uptake of Rb-86 was blunted by benz amil. Ribonuclease protection assay revealed I) a constitutive express ion of the mRNA encoding the oc-subunit of the epithelial Na+ channel and 2) that DXM increased the expression of this transcript. This incr ease was dose dependent and paralleled changes in transepithelial Natransport. This study suggests that a component of the beneficial effe ct of steroid therapy for the treatment of otitis media might be relat ed to increased fluid clearance.