Mechanism of Na‐H Exchanger‐1 Expression in Experimental Colitis: Role of Carbonic Anhydrase

Abstract

Na-H exchanger-1 (NHE-1) plays an important role in the neutral uptake of NaCl and water from GI-tract, and is suppressed in inflammatory bowel diseases (IBD). It is believed to be regulated by interaction of carbonic anhydrase (CA) with its C-terminal domain. Therefore in this study we investigated a role of CA in experimental colitis induced in rats by intra-rectal administration of trinitrobenzene sulphonic acid (TNBS). There are multiple CA isoforms which are expressed and regulated differently in various tissues. The isoforms CA-I and -II are cytoplasmic while the CA-IV is a membrane bound isoform. These isoforms are reported to express in the colon. In this study therefore we examined the level of CA isoforms -I, -II and -IV in colonic tissues taken from day 5 post colitis by western blot analysis. Colon was inflamed as indicated by elevation of MPO activity and tissue histology. There was suppression of protein levels of NHE-1, CA-1, -2 and -4 isoforms in the inflamed colon as compared to the non colitic controls. The levels of actin used as an internal control however remained unchanged in colitis. Since NHE-1 is fueled by protons which are produced by CA, a concomitant suppression of CA expression in inflamed colon suggests that NHE-1 is regulated by CA in colitis. Our findings discount the role of CA in contributing to an acidic pH of luminal contents reported in the IBD patients. Acknowledgment: A financial support from the Kuwait University is gratefully acknowledged.