HCO3— secretion is not impaired in inflamed mouse anterior proximal colon
One of the characteristics of inflammatory bowel disease (IBD) is an impaired, diminished or absent mucus barrier. For mucus to be effective in restricting commensal bacteria to the intestinal lumen, it must be expanded or hydrated. Mucus is secreted in a compacted state, and bound by H+ and Ca2+ ions, which shield the protein core of mucus consisting of many negative charges. A proposed mechanism for mucus expansion, is that HCO3— is secreted along with mucus into the intestinal lumen and it binds Ca2+ and neutralizes H+ ions. However, a recent study revealed a reduction in expression of the NaHCO3 cotransporter, NBCe1 in inflamed proximal colon. NBCe1 is thought to be involved in intestinal HCO3— secretion, therefore reduced secretion of HCO3— may be the cause of the impaired mucus barrier in IBD. To test this, we investigated whether HCO3— secretion was compromised in the proximal colon, specifically in the anterior proximal colon (APC), in an animal model of IBD, IL10-/- mice infected with Helicobacter typhlonius.By using the Ussing short circuit technique and pH stat technique, the electrogenic and electroneutral components of HCO3— secretion were measured. The results reveal that there was no appreciable electrogenic HCO3— secretion, and the majority of the electrogenic anion secretion, in the APC was a result of electrogenic Cl— secretion. In addition, although, electroneutral HCO3— secretion was present in the APC, it was very small, it was not stimulated by forskolin, and it was unaffected by inflammation.The results indicate that, little if any HCO3— secretion occurs in the anterior proximal colon, and that which does occur does not involve NBCe1. This suggests that the hydration of mucus in the proximal colon does not involve HCO3— and NBCe1 has some other role, possibly regulation of cell pH.
Advisor: Butt, Grant
Degree Name: Bachelor of Biomedical Sciences with Honours
Degree Discipline: Physiology
Publisher: University of Otago
Keywords: Bicarbonate secretion; IBD; Inflammatory bowel disease; electrogenic cl- secretion; electroneutral cl- secretion; electrogenic bicarbonate secretion; Ussing chamber; pH stat
Research Type: Thesis