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Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin–induced intestinal fluid secretion
Tonghui Ma, Jay R. Thiagarajah, Hong Yang, Nitin D. Sonawane, Chiara Folli, Luis J.V. Galietta, A.S. Verkman
Tonghui Ma, Jay R. Thiagarajah, Hong Yang, Nitin D. Sonawane, Chiara Folli, Luis J.V. Galietta, A.S. Verkman
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Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin–induced intestinal fluid secretion

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Abstract

Research Article

Authors

Tonghui Ma, Jay R. Thiagarajah, Hong Yang, Nitin D. Sonawane, Chiara Folli, Luis J.V. Galietta, A.S. Verkman

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Figure 4

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Specificity of CFTR inhibition by CFTRinh-172. (a) Alternative Cl– chann...
Specificity of CFTR inhibition by CFTRinh-172. (a) Alternative Cl– channels. Left: UTP (100 μM) stimulated Ca2+-dependent Cl– secretion measured in short-circuit current measurements on airway epithelial cells in the absence and presence of 5 μM CFTRinh-172. Right: Volume-activated Cl– current (hypotonic 250 mosM/kg H2O) measured in whole-cell patch-clamp experiments on FRT cells. Currents were recorded in the absence and presence of 5 μM CFTRinh-172. (b) MDR-1 activity. 3H-vincristine accumulation in 9HTEo-/Dx cells with upregulated MDR-1 expression. Intracellular vincristine was measured with and without verapamil (100 μM) or CFTRinh-172 (5 μM) (SE; n = 3). (c) ATP-sensitive K+ channels. Left: Representative membrane potential recording from a pancreatic β cell (INS-1) perfused extracellularly with CFTRinh-172, diazoxide (100 μM), and glibenclamide (glib; 10 μM). Right: Averaged changes in membrane potential (ΔmV) caused by indicated maneuvers (SE; n = 4). PD, potential difference.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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