Figure 10.

Integration of H₂O₂-activated regulatory signaling pathways. 1). H₂O₂ stimulates an increase in cytosolic Ca²⁺ concentration, which triggers two separate kinase pathways that are required for the overall inhibitory effect of H₂O₂ on Ca²⁺-dependent Cl⁻ secretion. 2). Whether these pathways influence different downstream transport processes or converge via a downstream signal is unknown. 3). H₂O₂ also inhibits basolateral Ca²⁺-responsive K⁺ efflux. 4). H₂O₂ inhibits NKCC1 activity independently of possible effects on apical Cl⁻ channels. 5). The inhibition of K⁺ efflux and NKCC1 activity likely contributes to the overall inhibitory effect of H₂O₂ on Ca²⁺-dependent ion transport in colonic epithelial cells.