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Chlorzoxazone or 1-EBIO Increases Na(+) Absorption Across Cystic Fibrosis Airway Epithelial Cells

Chlorzoxazone or 1-EBIO Increases Na(+) Absorption Across Cystic Fibrosis Airway Epithelial Cells

L Gao, J R Yankaskas, C M Fuller, E J Sorscher, S Matalon, H J Forman, C J Venglarik

Am J Physiol Lung Cell Mol Physiol. 2001 Nov;281(5):L1123-9.

PMID: 11597903

Abstract:

Previous studies demonstrated that chlorzoxazone or 1-ethyl-2-benzimidazolinone (1-EBIO) enhances transepithelial Cl(-) secretion by increasing basolateral K(+) conductance (G(K)) (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 Delta F508-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 microM) or 1-EBIO (2 mM) increased the amiloride-sensitive I(sc) approximately 2.5-fold. This overlapping specificity may preclude use of these compounds as CF therapeutics. Assaying for changes in the basolateral G(K) with a K(+) gradient plus the pore-forming antibiotic amphotericin B revealed that chlorzoxazone or 1-EBIO evoked an approximately 10-fold increase in clotrimazole-sensitive G(K). 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(K) alone can modulate epithelial Na(+) transport.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP10045451	1-EBIO		10045-45-1	Price

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