Contribution of Vasoactive Intestinal Peptide to the Depressant Effects of Glucagon-like Peptide-2 on Neurally Induced Contractile Responses in Mouse Ileal Preparations

Glucagon-like peptide-2 (GLP-2) has been reported to cause gastrointestinal relaxation by interfering with enteric inhibitory neurotransmitters, including vasoactive intestinal peptide (VIP). However, the involvement of VIP in the GLP-2's actions on isolated ileal preparations has never been explored. In this study, we investigated whether VIP contributes to the inhibitory effects of GLP-2 on spontaneous and neurally evoked contractions in mouse ileal segments. Functional experiments showed that VIP, as well as GLP-2, depresses both spontaneous and electrically induced contractile responses. The VIP antagonist, VIP 6-28, slightly increased the amplitude of the neurally induced contractile responses. VIP 6-28 did not alter the hormone's effects on the spontaneous activity, but reduced its inhibitory action on the neurally evoked contractions. In GLP-2-exposed specimens, immunohistochemistry showed a significant decrease in VIP-positivity in nerve fibers located in the muscle layers. These results provide the first evidence that in isolated mouse ileal preparations VIP contributes to the inhibitory effects of GLP-2 on the neurally induced contractile responses. From a physiological point of view, such depressant effects of the hormone may represent a mechanism aimed at slowing intestinal transit and optimizing nutrient absorption.