The Early Effect of Dextran Sodium Sulfate Administration on Carbachol-Induced Short-Circuit Current in Distal and Proximal Colon During Colitis Development

Abstract

Increased colonic Cl- secretion was supposed to be a causative factor of diarrhea in inflammatory bowel diseases. Surprisingly, hyporesponsiveness to Cl- secretagogues was later described in inflamed colon. Our aim was to evaluate changes in secretory responses to cholinergic agonist carbachol in distal and proximal colon during colitis development, regarding secretory activity of enteric nervous system (ENS) and prostaglandins. Increased responsiveness to carbachol was observed in both distal and proximal colon after 3 days of 2 % dextran sodium sulfate (DSS) administration. It was measured in the presence of mucosal Ba2+ to emphasize Cl- secretion. The described increase was abolished by combined inhibitory effect of tetrodotoxin (TTX) and indomethacin. Indomethacin also significantly reduced TTX-sensitive current. On the 7th day of colitis development responsiveness to carbachol decreased in distal colon (compared to untreated mice), but did not change in proximal colon. TTX-sensitive current did not change during colitis development, but indomethacin-sensitive current was significantly increased the 7th day. Decreased and deformed current responses to serosal Ba2+ were observed during colitis induction, but only in proximal colon. We conclude that besides inhibitory effect of DSS on distal colon responsiveness, there is an early stimulatory effect that manifests in both distal and proximal colon.

Properties of cholinergic and non‐cholinergic submucosal neurons along the mouse colon

“…Particular emphasis has been placed on examining the functional roles of the submucous plexus of the mouse colon (Buresi et al 2005;Hyland & Cox, 2005;Sorensen et al 2010;Okamoto et al 2012). This focus is possibly due to the relative ease of dissection of the murine colon compared to its small intestine, and considerable interest in examining colonic inflammation (MacNaughton et al 1998;Klompus et al 2010;Hock et al 2011;Juric et al 2013). However, the colonic regions examined in different studies often differ, which makes direct comparison between studies difficult, especially as there may be regional differences in the properties of submucosal neurons and in the epithelial responses between the proximal and distal colon of rodents (Cunningham & Lees, 1995;Cunningham et al 1997;Klompus et al 2010).…”