Chlorzoxazone or 1-EBIO increases Na+ absorption across cystic fibrosis airway epithelial cells

Academic Article


  • Previous studies demonstrated that chlorzoxazone or 1-ethyl-2-benzimidazolinone (1-EBIO) enhances transepithelial Cl secretion by increasing basolateral K conductance (G ) (Singh AK, Devor DC, Gerlach AC, Gondor M, Pilewski JM, and Bridges RJ. J Pharmacol Exp Ther 292: 778-787, 2000). Hence these compounds may be useful to treat cystic fibrosis (CF) airway disease. The goal of the present study was to determine whether chlorzoxazone or 1-EBIO altered ion transport across ΔF508-CF transmembrane conductance regulator homozygous CFT1 airway cells. CFT1 monolayers exhibited a basal short-circuit current that was abolished by apical amiloride (inhibition constant 320 nM) as expected for Na absorption. The addition of chlorzoxazone (400 μM) or 1-EBIO (2 mM) increased the amiloride-sensitive I ∼2.5-fold. This overlapping specificity may preclude use of these compounds as CF therapeutics. Assaying for changes in the basolateral G with a K gradient plus the pore-forming antibiotic amphotericin B revealed that chlorzoxazone or 1-EBIO evoked an ∼10-fold increase in clotrimazole-sensitive G . In contrast, chlorzoxazone did not alter epithelial Na channel-mediated currents across basolateral-permeabilized monolayers or in Xenopus oocytes. These data further suggest that alterations in basolateral G alone can modulate epithelial Na transport. - + + + + + K sc K K K
  • Digital Object Identifier (doi)

    Author List

  • Gao L; Yankaskas JR; Fuller CM; Sorscher EJ; Matalon S; Forman HJ; Venglarik CJ
  • Volume

  • 281
  • Issue

  • 5 25-5