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Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin–induced intestinal fluid secretion
Tonghui Ma, … , Luis J.V. Galietta, A.S. Verkman
Tonghui Ma, … , Luis J.V. Galietta, A.S. Verkman
Published December 1, 2002
Citation Information: J Clin Invest. 2002;110(11):1651-1658. https://doi.org/10.1172/JCI16112.
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Article

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 3

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Electrophysiological analysis of CFTR inhibition. (a) Left: CFTRinh-172 ...
Electrophysiological analysis of CFTR inhibition. (a) Left: CFTRinh-172 inhibition of short-circuit current (Isc) in permeabilized FRT cells expressing human CFTR. CFTR was stimulated by 100 μM CPT-cAMP. Right: Dose-inhibition data for CFTRinh-172 (circles) and glibenclamide (squares) (SE; n = 3 sets of experiments). (b) CFTRinh-172 inhibition of short-circuit current in primary culture of (nonpermeabilized) human bronchial epithelial cells. Inhibitor was added in apical bathing solution (left) or basolateral and then apical solutions (right). (c) Left: Whole-cell patch clamp of CFTR-expressing FRT cells showing membrane currents elicited at +80 mV (open circles) and –100 mV (filled circles). CFTR was stimulated by 5 μM forskolin followed by addition of 2 μM CFTRinh-172. The alternate stimulation was interrupted (I–III) for application of graded membrane potentials (middle). Right: Current-voltage relationships under basal conditions (control, open circles), after forskolin stimulation (filled circles), and following addition of 0.2 μM CFTRinh-172 giving approximately 50% inhibition (open triangles). Im, membrane current; Vm, membrane potential.

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