Mechanism of glucocorticoid-mediated reversal of inhibition of Cl−/ HCO 3 − exchange during chronic ileitis

In the normal ileum, coupled NaCl absorption occurs via the dual operation of Na+/H+ and Cl−/![Formula][1] exchange on the brush-border membrane (BBM) of villus cells. In a rabbit model of chronic small intestinal inflammation we determined the cellular mechanism of inhibition of NaCl absorption and the effect of steroids on this inhibition. Cl−/![Formula][2] but not Na+/H+ exchange was reduced in the BBM of villus cells during chronic ileitis. Cl−/![Formula][3] exchange was inhibited secondary to a decrease in the affinity for Cl− rather than an alteration in the maximal rate of uptake of Cl− (Vmax). Methylprednisolone (MP) stimulated Cl−/![Formula][4] exchange in the normal ileum by increasing the Vmax of Cl− uptake rather than altering affinity for Cl−. MP reversed the inhibition of Cl−/![Formula][5] exchange in rabbits with chronic ileitis. However, MP alleviated the Cl−/![Formula][6] exchange inhibition by restoring the affinity for Cl− rather than altering the Vmax of Cl− uptake. These data suggest that glucocorticoids mediate the alleviation of Cl−/![Formula][7] exchange inhibition in chronically inflamed ileum by reversing the same mechanism that was responsible for inhibition of this transporter rather than exerting a direct effect on the transporter itself, as was the case in normal ileum. [1]: /embed/mml-math-2.gif [2]: /embed/mml-math-3.gif [3]: /embed/mml-math-4.gif [4]: /embed/mml-math-5.gif [5]: /embed/mml-math-6.gif [6]: /embed/mml-math-7.gif [7]: /embed/mml-math-8.gif