Effects of Neural Blocking Agents on Motor Activity and Secretion in the Proximal and Distal Rat Colon: Evidence of Marked Segmental Differences in Nicotinic Receptor Activity

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Abstract
Background: Neuromodulation may be a new therapeutic approach in inflammatory bowel disease, but very little is known about neural control of colonic secretion in vivo. We therefore determined the effects of neural blockade on colonic motor activity and mucosal secretion in anaesthetized rats. Methods: A proximal and a distal colonic segment were isolated in four groups of chloralose-anaesthetized rats (n = 8 in each group), and we measured luminal pressure and transmural potential difference (PD) as a marker of electrogenic chloride secretion. Recordings were made from proximal and distal segments simultaneously, which made it possible to directly compare response patterns. Results: Under control conditions luminal pressure waves were associated with phasic, lumen-negative increases in PD which had a significantly greater magnitude and longer duration in the distal colon. Atropine blocked both pressure waves and PD waves in the proximal colon, but some PD waves, although of lower magnitude, remained in the distal colon. Hexamethonium abolished pressure waves in both segments and induced a marked reduction in PD in the distal but not in the proximal colon. Lidocaine also reduced PD, more so in the distal colon, and dissociated the pressure-PD linkage. Conclusion: In the distal but not in the proximal colon, there is a strong nicotinic, neurogenic `tone' that maintains a high basal secretory activity. The results encourage the search for neuromodulatory agents in the treatment of colonic secretory disease.