Mechanism of CFTR inhibition by diclofenac in T84 cells.

<p>(A) Schematic diagram illustrating the regulatory mechanisms of CFTR Cl⁻ channel activity in T84 cells. Inhibitors/activators used in this study are shown. PP, protein phosphatase; AMPK, AMP-activated protein kinase; PDE, phosphodiesterase; PKA, protein kinase A; AC, adenylate cyclase; MRP4, multidrug resistance-associated protein 4 (B) Involvements of PDE, MRP4, AMPK and protein phosphatase in the inhibition of CFTR-mediated Cl⁻ transport. Dose-inhibition studies of diclofenac were performed after the indicated treatments. Representative current tracings are shown. (C) Summary of dose-inhibition studies. Data are fitted to Hill equation and expressed as means of % agonist-stimulated apical Cl⁻ current ± S.E.M. (n = 6–8).