Glucagon-like-peptide-1 (GLP-1), an intestinal hormone, has been reported to slow gastric emptying and to reduce intestinal transit through vagal afferents and central nervous mechanisms. Because no data are available about a direct peripheral influence on gastrointestinal smooth muscle cells, the purpose of the present study was to investigate in vitro the effects of GLP-1 on the spontaneous and evoked mechanical activity of murine duodenum and colon, recording intraluminal pressure (index of the circular mechanical activity) and isometric tension (index of the longitudinal mechanical activity). In both intestinal segments GLP-1 (up to 1 mM) failed to affect the spontaneous mechanical activity; it caused a concentration-dependent reduction of the electrically-evoked cholinergic contractions in the circular muscular layer, without affecting the longitudinal muscle responses. GLP-1 failed to affect the concentration-responses curves for contractile effects evoked by exogenous carbachol suggesting that there was no change in the sensitivity of the muscarinic receptors. The GLP-1 inhibitory effect on neurally-evoked cholinergic contractions was significantly antagonized by exendin (9-39), an antagonist of GLP-1 receptors. In both intestinal preparations, GLP-1 effect was not affected by pretreatment with guanetidine, a blocker of adrenergic neurotransmission, but it was significantly reduced by Nw-Nitro-L-arginine, inhibitor of nitric oxide (NO)-synthase. The present results suggest that GLP-1 is able, acting peripherically on the intestinal segments, to modulate negatively the excitatory cholinergic neurotransmission through prejunctional GLP-1 receptors. The inhibitory effect of GLP-1 seems to involve NO production.

Supported by PRIN 2007