Glucocorticosteroids increase sodium transport in middle ear epithelium.
The effect of glucocorticosteroids on ion transport was investigated on a middle ear cell line with the short-circuit current (Isc) technique. Dexamethasone (DXM) produced a dose- and time-dependent increase in Isc. 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 medium. 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 86Rb was blunted by benzamil. Ribonuclease protection assay revealed 1) a constitutive expression of the mRNA encoding the alpha-subunit of the epithelial Na+ channel and 2) that DXM increased the expression of this transcript. This increase was dose dependent and paralleled changes in transepithelial Na+ transport. This study suggests that a component of the beneficial effect of steroid therapy for the treatment of otitis media might be related to increased fluid clearance.
Herman
P
P
Laboratoire d'Otologie Expérimentale, Faculté Lariboisiere, St. Louis, Université Paris VII, France.
Tan
C T
CT
van den Abbeele
T
T
Escoubet
B
B
Friedlander
G
G
Huy
P T
PT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004432:Ear, Middle / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005849:Gerbillinae; D007425:Intracellular Membranes / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D012333:RNA, Messenger; D015222:Sodium Channels; D010042:Ouabain; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium