Acid-base effects on intestinal Cl-absorption and vesicular trafficking

Abstract

In rat ileum and colon, apical membrane [Formula: see text] exchange and net Cl-absorption are stimulated by increases in Pco2or [Formula: see text]. Because changes in Pco2stimulate colonic Na+absorption, in part, by modulating vesicular trafficking of the Na+/H+exchanger type 3 isoform to and from the apical membrane, we examined whether changes in Pco2affect net Cl-absorption by modulating vesicular trafficking of the [Formula: see text] exchanger anion exchanger (AE)1. Cl-transport across rat distal ileum and colon was measured in the Ussing chamber, and apical membrane protein biotinylation of these segments and Western blots of recovered proteins were performed. In colonic epithelial apical membranes, AE1 protein content was greater at Pco270 mmHg than at Pco221 mmHg but was not affected by pH changes in the absence of CO2. AE1 was internalized when Pco2was reduced and exocytosed when Pco2was increased, and both mucosal wortmannin and methazolamide inhibited exocytosis. Wortmannin also inhibited the increase in colonic Cl-absorption caused by an increase in Pco2. Increases in Pco2stimulated ileal Cl-absorption, but wortmannin was without effect. Ileal epithelial apical membrane AE1 content was not affected by Pco2. We conclude that CO2modulation of colonic, but not ileal, Cl-absorption involves effects on vesicular trafficking of AE1.