The incretin hormone glucagon-like peptide-1 (GLP-1), released from intestinal enteroendocrine L cells after meal ingestion, reduces gastric emptying and promotes satiety by binding a specific receptor (GLP-1R). The peptide modulation on the gastrointestinal motility appears to be due mainly to central nervous mechanisms, but recently involvement of the enteric nervous system has been also shown. Because it's not known if GLP-1 slows gastric emptying exclusively through extrinsic neural pathways, the aim of this study was to investigate GLP-1 mechanical effects on mouse isolated whole stomach and on carbachol (CCh)-precontracted fundic and antral circular muscular strips, using the organ bath technique. In addition, the distribution of GLP-1R in the gastric regions was examined by RT-PCR.

In the whole stomach GLP-1 produced a concentration-dependent relaxation that was significantly antagonized by exendin (9–39) or by Nw-nitro-L-arginine methyl ester (L-NAME) and was abolished by tetrodotoxin (TTX). In CCh-precontracted antral strips, GLP-1 induced inhibitory effects abolished by TTX and significantly antagonized by L-NAME, while it was without any effect in CCh-precontracted fundic strips. RT-PCR showed that GLP-1R mRNA was present exclusively in antral tissue but not in gastric fundus.

In conclusion, our results provide evidence for ability of GLP-1 of reducing gastric motility by acting peripherally in the antral region through neural NO release.

Supported by PRIN 2007