GLUCAGON-LIKE PEPTIDE-1 MODULATES EXCITATORY CHOLINERGIC NEUROTRANSMISSION OF MOUSE DUODENUM AND COLON

The incretin Glucagon-like-peptide-1 (GLP-1) is produced by enterendocrine L cells of the small intestine. It delays gastric emptying and reduces intestinal transit by inhibiting vagal activity. To date, no evidences 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 μM) did not affect spontaneous mechanical activity while it caused a concentration-dependent reduction of electrically-evoked cholinergic contractions of circular muscular layer, but not of longitudinal muscle. The GLP-1 inhibitory effect on neurally-evoked cholinergic contractions was significantly antagonized by the GLP-1 receptors antagonist exendin (9-39). 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 Nω-Nitro-L-arginine, inhibitor of nitric oxide (NO)-synthase. The present results suggest that GLP-1 is able to modulate negatively the excitatory cholinergic neurotransmission acting peripherically through prejunctional GLP-1 receptors. The inhibitory effect of GLP-1 seems to involve NO production.