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Titolo:
Chlorzoxazone or 1-EBIO increases Na+ absorption across cystic fibrosis airway epithelial cells
Autore:
Gao, L; Yankaskas, JR; Fuller, CM; Sorscher, EJ; Matalon, S; Forman, HJ; Venglarik, CJ;
Indirizzi:
Univ Alabama, Dept Environm Hlth Sci, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 m Hlth Sci, Birmingham, AL 35294 USA Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 & Biophys, Birmingham, AL 35294 USA Univ Alabama, Dept Med, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 , Dept Med, Birmingham, AL 35294 USA Univ Alabama, Dept Anesthesiol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 nesthesiol, Birmingham, AL 35294 USA Univ Alabama, Dept Comparat Med, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 mparat Med, Birmingham, AL 35294 USA Univ N Carolina, Dept Pulm & Crit Care Med, Chapel Hill, NC 27599 USA UnivN Carolina Chapel Hill NC USA 27599 e Med, Chapel Hill, NC 27599 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
fascicolo: 5, volume: 281, anno: 2001,
pagine: L1123 - L1129
SICI:
1040-0605(200111)281:5<L1123:CO1INA>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
BASOLATERAL-K CONDUCTANCE; TURTLE COLON; CL SECRETION; INTERMEDIATE-CONDUCTANCE; CHANNELS; TRANSPORT; ACTIVATION; CFTR; AMILORIDE; REGULATOR;
Keywords:
epithelial sodium channel; cystic fibrosis transmembrane conductance regulator; clotrimazole; amiloride; 1-ethyl-2-benzimidazolinone;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Venglarik, CJ Univ Alabama, Dept Environm Hlth Sci, 760 McCallum,1918 UnivBlvd, Birmingham, AL 35294 USA Univ Alabama 760 McCallum,1918 Univ Blvd Birmingham AL USA 35294
Citazione:
L. Gao et al., "Chlorzoxazone or 1-EBIO increases Na+ absorption across cystic fibrosis airway epithelial cells", AM J P-LUNG, 281(5), 2001, pp. L1123-L1129

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 muM) or 1-EBIO (2 mM) increased the amiloride-sensitive I-sc similar to2.5-fold. This overlapping specificity may preclude use of these compounds asCF 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 similar to 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 23:48:04