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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 5

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Inhibition of intestinal fluid secretion. (a) Photograph of isolated mou...
Inhibition of intestinal fluid secretion. (a) Photograph of isolated mouse ileal loops at 6 hours after lumenal injection of 1 μg cholera toxin without (top) and with (middle) intraperitoneal injection of CFTRinh-172 (250 μg/kg). Saline control (no cholera toxin) is shown for comparison (bottom). (b) Ileal loop weight at 6 hours. Mean ± SE (n = 6–8 mice) with 14–16 loops studied. For the inactive analog, the 4-carboxyphenyl substituent in CFTRinh-172 was replaced by 3-methoxy-4-methoxyvinylphenyl (SE; six to eight mice per group; *P < 0.001, ANOVA). (c) Ratio of weight of entire small intestine at 6 hours after oral gavage before versus after luminal fluid removal (SE; four mice per group; *P < 0.001). (d) CFTRinh-172 inhibition short-circuit current after amiloride addition and stimulation by forskolin (20 μM) in isolated rat colonic mucosa. CFTRinh-172 was added to serosal and then mucosal surfaces as indicated. One experiment typical of four is shown.

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