Omeprazole decreased paracellular cation selectivity.
Similar to previous reports[21,22], Caco-2 monolayers showed high PNa/PCl (3.79 ± 0.15 in 14 d monolayers; 3.96
± 0.22 in 21 d monolayers) from the higher PNa (8.28 ± 0.20 in 14 d monolayers; 8.11 ± 0.25 in 21 d monolayers) than
PCl (2.08 ± 0.09 in 14 d monolayers; 2.07 ± 0.11 in 21 d monolayers) (Figure 4A-C). Therefore, the Caco-2 monolayer was a cation selective epithelium. In 14 d- as well as 21 d-omeprazole-treated groups, omeprazole significantly suppressed PNa/PCl and PNa but enhanced PCl in a dosedependent manner (Figure 4A-C), indicating that omeprazole decreased cation selectivity of Caco-2 monolayers. Moreover, the present study also examined the paracellular permeability to monovalent cations, i.e. Li+, Na+,K+, Rb+, and Cs+. In control conditions, Caco-2 monolayers
showed the following selective sequence: PNa (8.62
± 0.18) > PK (7.99 ± 0.19) > PRb (5.84 ± 0.08) > PCs (4.82
± 0.07) > PLi (3.98 ± 0.12) (Figure 4D). Interestingly, 14
d-omeprazole (600 ng/mL)-exposed monolayers showed
a different permeability sequence as follows: PK > PNa >
PRb > PCs > PLi (Figure 4D). In addition, omeprazole also
inhibited Caco-2 permeability to all of these monovalent
cations in a dose-dependent manner. In a parallel study, TER was simultaneously recorded
when the monolayers were exposed to group I alkaline
metals containing solution. In control conditions, Caco-2
monolayers showed the highest conductance (lowest
TER) to Na+ (Figure 4E). The TER-Pauling radii relationship
showed a V-shaped profile. Omeprazole-treated
Caco-2 monolayers showed the lowest TER when the primary
ion was K+ (Figure 4E). Omeprazole also changed
the TER-Pauling radii graph to a U-shape relationship and
increased TER in all groups.