Aim: 

Glucagon-like peptide-2 (GLP-2) is a hormone affecting multiple aspects of gastrointestinal physiology. So far, it has not been clarified yet whether GLP-2 has a peripheral direct influence on the gastric emptying. Therefore, we tested the hypothesis that GLP-2 may affect gastric tone of the isolated mouse whole organ. In addition, we examined the mechanism of action responsible for the observed effects.

Methods: 

The effects of the GLP-2 on the mouse spontaneous gastric mechanical activity were analysed in vitro, recording the intraluminal pressure.

Results: 

GLP-2 (1 nM – 0.3 mM) produced a concentration-dependent relaxation which reached the 75% of the relaxation induced by isoproterenol (1 mM). The inhibitory effects of the peptide were virtually abolished by desensitization of GLP-2 receptors and by a-chymotrypsin. The relaxant response to GLP-2 was not affected by tetrodotoxin, a blocker of neuronal voltage-dependent Na⁺ channels, but it was significantly reduced by w-conotoxin GVIA, a blocker of neuronal N type voltage-operated Ca²⁺ channels. N_w-nitro-L-arginine methyl ester (L-NAME), a blocker of nitric oxide synthase, or apamin, a blocker of small conductance Ca²⁺-dependent potassium channels, failed to affect the gastric response to the peptide. The relaxation to GLP-2 was virtually abolished by desensitization of the vasoactive intestinal peptide (VIP) receptors.

Conclusions: 

These results provide the first experimental evidence that GLP-2 is able to induce gastric relaxation acting peripherally on the mouse stomach. The effect appears to be mediated by prejunctional neural release of VIP.