Role of Carbonic Anhydrase in the Regulation of Na‐H exchanger‐1 in Experimental Colitis

Abstract

A role of carbonic anhydrase (CA) was investigated in the regulation of Na–H exchanger‐1 (NHE‐1) in experimental colitis. Trinitrobenzenesulphonic acid (TNBS) was administered intra‐rectally to induce colitis in rats, and the animals were sacrificed on day 6 post TNBS. The isoforms CA‐I and CA‐II were the abundant isoforms in the colon but expressed as minor ones in the ileum. Both CA isoforms, on co‐immunoprecipitation and confocal microscopy, appeared to be colocalized with the NHE‐1 isoform in the colon. Importantly, inflammation reduced the expression of these proteins in the colon, but not in the ileum. The reduction in the level of co‐immunoprecipitated CA isoforms was more pronounced as compared to their level of expression in the inflamed tissue. Ex‐vivo treatment of uninflamed colonic strips by TNF‐α reduced the expression of CA isoforms. The binding site of the CA‐II isoform was identified in a peptide (83 aa) selected from the NHE‐1 C‐terminus. However, the CA‐I isoform did not bind with the same peptide. Since the tissues used in this study expressed inflammatory markers, the present data suggest that the uncoupling of CA and NHE‐1 is due to inflammation. This uncoupling would lead to a reduction in the NHE‐1 activity and an accumulation of H+ intracellularly, which together cause acidosis and necrosis in the inflamed colon in the present model.Support or Funding InformationResearch Sector, Kuwait University, Kuwait (Grant # MB03/15)