Figure 1. Effects of diclofenac on cAMP-activated Cl⁻ secretion in T84 cells.

(A) A model of Cl⁻ secretion by an enterocyte showing transport proteins involved in transepithelial Cl⁻ secretion. CFTR, cystic fibrosis transmembrane conductance regulator; IRC, inwardly rectifying Cl⁻ channel; CaCC, Ca²⁺-activated Cl⁻ channel; KCNQ1/KCNE3, cAMP-activated K⁺ channel; K_Ca3.1, Ca²⁺-activated K⁺ channel. (B) CFTR mediated cAMP-activated Cl⁻ secretion induced by forskolin. A representative short-circuit current tracing is shown (n = 5). (C) Effect of diclofenac on cAMP-activated Cl⁻ secretion. Diclofenac at the indicated concentrations was added into both apical and basolateral solutions (n = 4). (D) Polarity of inhibition by diclofenac on cAMP-activated Cl⁻ secretion. Diclofenac at the indicated concentrations was sequentially added into basolateral and apical solutions, respectively. A representative short-circuit current tracing is shown (n = 5). (E) The inhibition by diclofenac does not require metabolic activation. T84 cell monolayers were pretreated with 1-ABT, an inhibitor of CYP enzymes (1 mM). Diclofenac at the indicated concentrations was added into both apical and basolateral solutions. A representative short-circuit current tracing is shown (n = 5).