Hydrogen peroxide inhibits cAMP-induced Cl−secretion across colonic epithelial cells

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Abstract
We examined the effects of H2O2on Cl−secretion across human colonic T84 cells grown on permeable supports and mounted in modified Ussing chambers. Forskolin-induced short-circuit current, a measure of Cl−secretion, was inhibited in a concentration-dependent fashion when monolayers were pretreated with H2O2for 30 min (30–100% inhibition between 500 μM and 5 mM). Moreover, H2O2inhibited 76% of the Cl−current across monolayers when the basolateral membranes were permeabilized with nystatin (200 μg/ml). When the apical membrane was permeabilized with amphotericin B, H2O2inhibited the Na+current (a measure of Na+-K+-ATPase activity) by 68% but increased the K+current more than threefold. In addition to its effects on ion transport pathways, H2O2also decreased intracellular ATP levels by 43%. We conclude that the principal effect of H2O2on colonic Cl−secretion is inhibitory. This may be due to a decrease in ATP levels following H2O2treatment, which subsequently results in an inhibition of the apical membrane Cl−conductance and basolateral membrane Na+-K+-ATPase activity. Alternatively, H2O2may alter Cl−secretion by direct action on the transporters or alterations in signal transduction pathways.