Tetracyclines reduce Na+/K+ pump capacity in Calu-3 human airway cells.
We studied the effect of tetracyclines on the Na+/K+ pump activity in Calu-3, a human airway cell line. To estimate Na+/K+ pump capacity on the basolateral membrane, an ouabain-sensitive component of the short-circuit current (Isc) was measured in the presence of nystatin, an ionophore of Na+. The application of ouabain (1 mM) to the basolateral solution completely inhibited the Isc generated by adding nystatin (50 microM) to the apical solution. Tetracycline (TC), minocycline (MC), or demethylchlortetracycline (DC) at 0.5 mM applied to the apical but not to the basolateral solution also decreased the nystatin-induced Isc. Neither phlorizin- nor diphenylamine-2-carboxylic acid-sensitive Isc was affected by TC, MC, or DC. These results indicate that tetracyclines may permeate only through the apical membrane with the result that the Na+/K+ pump's capacity for Na+ extrusion should be suppressed without a decrease in Cl- transport.
Ito
Y
Y
2nd Department of Internal Medicine, School of Medicine, Nagoya University, Tsurumai-cho, Showa-ku, 466, Japan. itoyasu@tsuru.med.nagoya-u.ac.jp
Kume
H
H
Yamaki
K
K
Takagi
K
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001980:Bronchi / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D003707:Demeclocycline / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008911:Minocycline / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*; D013997:Time Factors; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007476:Ionophores; D062367:ortho-Aminobenzoates; D009761:Nystatin; D010042:Ouabain; D003707:Demeclocycline; C001209:fenamic acid; D010695:Phlorhizin; D000254:Sodium-Potassium-Exchanging ATPase; D008911:Minocycline; D006851:Hydrochloric Acid