{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:25:50Z","timestamp":1765182350045,"version":"3.46.0"},"reference-count":51,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004434","name":"University of Florence ex-60%","doi-asserted-by":"publisher","award":["RI-CATEN25"],"award-info":[{"award-number":["RI-CATEN25"]}],"id":[{"id":"10.13039\/501100004434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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\u201328, slightly increased the amplitude of the neurally induced contractile responses. VIP 6\u201328 did not alter the hormone\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms262411797","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:21:43Z","timestamp":1765182103000},"page":"11797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contribution of Vasoactive Intestinal Peptide to the Depressant Effects of Glucagon-like Peptide-2 on Neurally Induced Contractile Responses in Mouse Ileal Preparations"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4665-1426","authenticated-orcid":false,"given":"Maria Caterina","family":"Baccari","sequence":"first","affiliation":[{"name":"Section of Physiological Sciences, Department of Experimental & Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donata","family":"Conti","sequence":"additional","affiliation":[{"name":"Research Unit of Histology & Embryology, Department of Experimental & Clinical Medicine, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-5025","authenticated-orcid":false,"given":"Maria Giuliana","family":"Vannucchi","sequence":"additional","affiliation":[{"name":"Research Unit of Histology & Embryology, Department of Experimental & Clinical Medicine, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2756-6552","authenticated-orcid":false,"given":"Eglantina","family":"Idrizaj","sequence":"additional","affiliation":[{"name":"Section of Physiological Sciences, Department of Experimental & Clinical Medicine, University of Florence, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1146\/annurev-physiol-021113-170317","article-title":"Physiology and Pharmacology of the Enteroendocrine Hormone Glucagon-like Peptide-2","volume":"76","author":"Drucker","year":"2014","journal-title":"Annu. 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