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


METHODS
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 microg/mL) to the mucosal side decreased short-circuit current (Isc) from 14.4 +/- 1.3 to 5.6 +/- 0.6 microA/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.
First Department of Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
S
S
Kanoh
J
J
Tamaoki
M
M
Kondo
A
A
Nagai
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D002417:Cattle; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology*; D004553:Electric Conductivity; D024841:Fluoroquinolones; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D010879:Piperazines / Q000493:pharmacokinetics*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D013183:Sputum / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000890:Anti-Infective Agents; D002712:Chlorides; D024841:Fluoroquinolones; D010879:Piperazines; C075375:grepafloxacin