The gut hormone glucagon-like peptide-2 (GLP-2) affects multiple facets of gastrointestinal (GI) physiology, including growth, absorption and motility through the interaction with a G-protein-linked receptor (GLP-2R). The aims of present study were to examine: i) The expression GLP-2R in the mouse GI tract; ii) the effects of GLP-2 on the spontaneous mechanical activity and on neurally-mediated responses in proximal colon; iii) the mechanism responsible for the effects observed.

GLP-2R protein expression was higher in gastric fundus and colon than in the small bowel. In proximal colon, GLP-2 produced a concentration-dependent reduction of the spontaneous contractions, detected as changes in endoluminal pressure. This effect was significantly reduced by the desensitization of GLP-2R, atropine or pertussis toxin (PTX) and it was abolished by tetrodotoxin. GLP-2 also caused a reduction of the electrically-evoked cholinergic contractions, without affecting the inhibitory neural response. Once more, the inhibitory action of GLP-2 was significantly reduced by GLP-2R desensitization or by PTX. The peptide failed to affect the contractile effects evoked by exogenous carbachol.

In conclusion, in mouse proximal colon, GLP-2 is able to modulate negatively the spontaneous mechanical activity and the electrically-evoked cholinergic contractions through inhibition of acetylcholine release, mediated by activation of inhibitory G protein.

Supported by PRIN2007