Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 26, Issue 2, Pages 237-246Publisher
WILEY-BLACKWELL
DOI: 10.1111/nmo.12254
Keywords
adenosine triphosphate; colon; enterochromaffin cell; ileum; mechanosensory; purinergic; serotonin
Funding
- EPSRC [EP/J000175/1]
- Royal Society
- University of Brighton
- EPSRC [EP/J000175/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/J000175/1] Funding Source: researchfish
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BackgroundMechanical stimulation of the mucosal epithelium results in increased serotonin (5-HT) release from enterochromaffin (EC) cells. Little is known about how this process varies in different regions of the intestinal tract; however, purines are felt to play a role. We studied the relationship between mechanical stimulation, adenosine triphosphate (ATP), and 5-HT release from ileal and colonic mucosal tissue. MethodsAmperometric recordings of ATP and 5-HT were carried out using an ATP biosensor and boron-doped diamond microelectrode. Levels of extracellular ATP and 5-HT were monitored using high performance liquid chromatography. Key ResultsUnder basal conditions, 5-HT levels were significantly decreased in the ileum (p<0.001) but not the colon in the presence of the P2 antagonist suramin (100M). Ecto-ATPase inhibitor ARL67156 (10M) elevated ATP levels in the ileum and colon (both p<0.001), but only 5-HT levels in the ileum (p<0.001). Exogenous ATP increased 5-HT release in the presence of tetrodotoxin in the ileum (p<0.001), but had not effect in the colon. Mechanical stimulation increased levels of 5-HT in the ileum (p<0.001) and colon (p<0.01), but levels returned to baseline in the presence of suramin and MRS2179 in the ileum. The onset of 5-HT release was delayed following mechanical stimulation. The rise time of the ATP response was quicker than that of 5-HT during mechanical stimulation. Conclusions & InferencesDuring mechanical stimulation of the mucosal epithelium, ATP mediates 5-HT release from EC cells in the ileum, but not the colon. Mucosal 5-HT signaling following mechanical stimulation is varied in different regions of the intestinal tract.
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