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Inhibition of CFTR-mediated intestinal chloride secretion by nornidulin: Cellular mechanisms and anti-secretory efficacy in human intestinal epithelial cells and human colonoids

Fig 3

The polarity of inhibition by nornidulin on cAMP-induced Cl secretion in T84 cells.

(A) Shows a representative short-circuit current (Isc) trace. In this experiment, nornidulin was applied at various concentrations to both the basolateral and apical sides of the cell layer after stimulation with FSK (n = 5). (B) Illustrates the dose-dependent response of nornidulin on CFTR-mediated apical chloride current (ICl-) in T84 cells. Before activating CFTR with FSK, the basolateral membrane was first made permeable by using amphotericin B (250 μg/mL for 30 minutes). Nornidulin was then added to the apical side at different concentrations. The graph shows a representative trace of the apical chloride current (ICl-) (n = 5). (C) Western blot analysis of CFTR protein expression in T84 cells after 24-h exposure to nornidulin (5 μM) (n = 8). ns, non-significant compared with control.

Fig 3

doi: https://doi.org/10.1371/journal.pone.0314723.g003