Hydrogen peroxide inhibits cAMP-induced Cl- secretion across colonic epithelial cells.
We examined the effects of H2O2 on 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 H2O2 for 30 min (30-100% inhibition between 500 microM and 5 mM). Moreover, H2O2 inhibited 76% of the Cl- current across monolayers when the basolateral membranes were permeabilized with nystatin (200 micrograms/ml). When the apical membrane was permeabilized with amphotericin B, H2O2 inhibited 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, H2O2 also decreased intracellular ATP levels by 43%. We conclude that the principal effect of H2O2 on colonic Cl- secretion is inhibitory. This may be due to a decrease in ATP levels following H2O2 treatment, which subsequently results in an inhibition of the apical membrane Cl- conductance and basolateral membrane Na+-K+-ATPase activity. Alternatively, H2O2 may alter Cl- secretion by direct action on the transporters or alterations in signal transduction pathways.
DuVall
M D
MD
Department of Anesthesiology, University of Alabama, Birmingham, Alabama 34294, USA.
Guo
Y
Y
Matalon
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000666:Amphotericin B / Q000494:pharmacology; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D003106:Colon / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D004553:Electric Conductivity; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase; D008564:Membrane Potentials; D009761:Nystatin / Q000494:pharmacology
D002712:Chlorides; D009761:Nystatin; D005576:Colforsin; D000666:Amphotericin B; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase