Protection by tetracyclines against ion transport disruption caused by nystatin in human airway epithelial cells.
Polyene antifungal antibiotics like nystatin form monovalent cation pores on the plasma membrane that perturb the intracellular electrolyte milieu, resulting in cell damage. In the present study, we investigated the effects of tetracyclines (minocycline and tetracycline) on ion transporters disrupted by nystatin in cultured human airway Calu-3 cells. Apical application of nystatin (50 microM) on a monolayer of the cells stimulated Na(+)-K(+) pump activity as estimated by ouabain (1 mM)-sensitive short-circuit current (I(sc)). The nystatin-potentiated I(sc) was inhibited by minocycline (IC(50) = 25 microM) or tetracycline (IC(50) = 150 microM) applied only from the apical (nystatin-treated) side. Nystatin increased monolayer conductance that was reversed by the application of tetracyclines. In contrast, ouabain potentiated the nystatin-induced change in the conductance. Further, Na(+)-glucose transport affected by nystatin was also normalized by tetracyclines from the nystatin-treated side of the membrane. These data suggest that tetracyclines may lower the cell permeability potentiated by nystatin, protecting cells against damage.
Ito
Y
Y
Second Division (Respiratory Division), First Department of Physiology, School of Medicine, Nagoya University, Tsurumai-cho, Nagoya, 466-8550, Japan. itoyasu@med.nagoya-u.ac.jp
Nakayama
S
S
Son
M
M
Kume
H
H
Yamaki
K
K
D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008911:Minocycline / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000187:drug effects; D009761:Nystatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010042:Ouabain / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D013754:Tetracyclines / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009004:Monosaccharide Transport Proteins; D013754:Tetracyclines; D009761:Nystatin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D013752:Tetracycline; D008911:Minocycline