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This Article Full Text Full Text (PDF) All Versions of this Article: 89/4/417    most recent expphysiol.2003.027003v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, X. F. Articles by Quinton, P. M. Search for Related Content PubMed PubMed Citation Articles by Wang, X. F. Articles by Quinton, P. M. Related Collections GI & Epithelial

¹ Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0831, USA² Division of Biomedical Sciences, University of California Riverside, CA 92521-0121, USA

Effective and specific inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl^– channel in epithelia has long been needed to better understand the role of anion movements in fluid and electrolyte transport. Until now, available inhibitors have required high concentrations, usually in the millimolar or high micromolar range, to effect even an incomplete block of channel conductance. These inhibitors, including 5-nitro-2(3-phenylpropyl-amino)benzoate (NPPB), bumetamide, glibenclamide and DIDS, are also relatively non-specific. Recently a new anion channel inhibitor, a thiazolidinone derivative, termed CFTR_Inh-172 has been synthesized and introduced with apparently improved inhibitory properties as shown by effects on anion conductance expressed in cell lines and on secretion in vivo. Here, we assay the effect of this inhibitor on a purely salt absorbing native epithelial tissue, the freshly isolated microperfused human sweat duct, known for its inherently high expression of CFTR. We found that the inhibitor at a maximum dose limited by its aqueous solubility of 5 µM partially blocked CFTR when applied to either surface of the membrane; however, it may be somewhat more effective from the cytosolic side (70% inhibition). It may also partially inhibit Na⁺ conductance. The inhibition was relatively slow, with a half time for maximum effect of about 3 min, and showed very slow reversibility. Results also suggest that CFTR Cl^– conductance (G_Cl) was blocked in both apical and basal membranes. The inhibitor appears to exert some effect on Na⁺ transport as well.

(Received 19 January 2004; accepted after revision 19 April 2004; first published online 6 May 2004)
Corresponding author P. M. Quinton: Department of Pediatrics, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0831, USA. Email: pquinton{at}ucsd.edu

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