New quinolone, grepafloxacin, inhibits Cl− secretion across bovine airway epithelium in culture

Abstract

Objective: Transepithelial ion transport plays an important role in the regulation of the amount and the rheological properties of bronchial secretion. The effect of grepafloxacin (GPFX), a new quinolone agent, on bioelectrical properties of airway epithelium was determined.Methodology: Electrical properties of bovine tracheal epithelium cultured under an air–liquid interface condition were measured by the short‐circuit technique.Results: Addition of GPFX (100 μg/mL) to the mucosal side decreased short‐circuit current (Isc) from 14.4 ± 1.3 to 5.6 ± 0.6 μA/ cm2 (P < 0.001), and the response was accompanied by corresponding decreases in transepithelial potential difference and cell conductance. This effect was concentration dependent, and a similar response was also noted when GPFX was added to the submucosal side. The GPFX‐induced decrease in Isc was not altered by the Na+ channel blocker amiloride, but was inhibited by the Cl− channel blocker diphenylamine‐2‐carboxylate or Cl−‐free medium (P < 0.001, in each case). Furthermore, GPFX reduced Cl− conductance (P < 0.01) without affecting Na+ conductance of the epithelium.Conclusions: Grepafloxacin selectively inhibits Cl− secretion across tracheal epithelial cells, which may result in the inhibition of water secretion and, hence, the reduction of airway secretion.