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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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

¹Nephrology Section, ²Research Service, and ³Department of Pathology, Veterans Affairs Medical Center, New York University School of Medicine, New York, New York 10010

Submitted 20 October 2003 ; accepted in final form 23 December 2003

In rat ileum and colon, apical membrane exchange and net Cl^- absorption are stimulated by increases in PCO₂ or . Because changes in PCO₂ stimulate 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 PCO₂ affect net Cl^- absorption by modulating vesicular trafficking of the 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 PCO₂ 70 mmHg than at PCO₂ 21 mmHg but was not affected by pH changes in the absence of CO₂. AE1 was internalized when PCO₂ was reduced and exocytosed when PCO₂ was 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 PCO₂ stimulated ileal Cl^- absorption, but wortmannin was without effect. Ileal epithelial apical membrane AE1 content was not affected by PCO₂. We conclude that CO₂ modulation of colonic, but not ileal, Cl^- absorption involves effects on vesicular trafficking of AE1.

PCO₂; ileum; colon; anion exchanger 1; Na⁺/H⁺ exchanger type 3

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