{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:30:27Z","timestamp":1778239827211,"version":"3.51.4"},"reference-count":78,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["UIDP\/04539\/2020 (CIBB)"],"award-info":[{"award-number":["UIDP\/04539\/2020 (CIBB)"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Background: Gastrointestinal (GI) disturbances occur frequently in the early premotor stage of Parkinson\u2019s disease (PD). These GI impairments are associated, at least in part, with dopaminergic dysfunction in the myenteric plexus. However, the enteric nervous system (ENS) pathophysiology underlying GI dysfunction in PD has been overlooked. Objectives: The aim of this study was to evaluate the premotor GI disturbances in rats submitted to intranasal (i.n.) MPTP, a valid experimental model of the premotor stage of PD. Methods: Ileum segments from male Wistar rats (21 weeks old) were collected 12 days following the i.n. MPTP administration for functional studies. Isometric contractile concentration\u2013response (CR) curves (cumulative) for dopamine (DA) were performed in both the presence and absence of sulpiride, a selective dopamine D2-like receptor (D2R) antagonist. Results: Functional studies showed that DA induced a concentration-dependent contractile response in the ileum, which exhibited marked contraction at lower concentrations (0.01\u20130.9 \u00b5M) and relaxation at higher concentrations (3\u201390 \u00b5M). MPTP significantly attenuated both the contraction and the ensuing relaxation. Furthermore, sulpiride significantly reduced the contractile response to DA in the control group and blocked the relaxation in the MPTP group. The MPTP-induced dysmotility occurred with preserved DA homeostasis, as shown by normal DA, TH, and D2R ileal levels in the MPTP group. However, MPTP seemed to impose a decrease in S100\u03b2 and GFAP (enteroglial markers) immunostaining in the ileal myenteric plexus. Conclusions: In summary, we provide pioneering functional, neurochemical, and morphological evidence showing that rats submitted to the i.n. MPTP model exhibited premotor DA-dependent ileum motile dysfunction accompanied by enteroglial disturbance within the myenteric plexus, but with preserved DA markers.<\/jats:p>","DOI":"10.3390\/biomedicines13102400","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:16:29Z","timestamp":1759241789000},"page":"2400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intranasal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration Hampered Contractile Response of Dopamine in Isolated Rat Ileum"],"prefix":"10.3390","volume":"13","author":[{"given":"Ana","family":"Silva","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1316-1319","authenticated-orcid":false,"given":"Sofia","family":"Viana","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Coimbra Health School, Health and Technology Research Center (H&TRC), Polytechnic University of Coimbra, 3046-854 Coimbra, Portugal"}]},{"given":"In\u00eas","family":"Pita","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Cristina","family":"Lemos","sequence":"additional","affiliation":[{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Department of Psychiatry, University of Innsbruck, 6020 Innsbruck, Austria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-5954","authenticated-orcid":false,"given":"Filipe C.","family":"Matheus","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florian\u00f3polis 88040-900, Brazil"}]},{"given":"Lina","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Institute of Anatomical and Molecular Pathology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9707-4895","authenticated-orcid":false,"given":"Carlos A.","family":"Fontes Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7547-6463","authenticated-orcid":false,"given":"Rui D.","family":"Prediger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), Florian\u00f3polis 88040-900, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-3320","authenticated-orcid":false,"given":"Frederico C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-8651","authenticated-orcid":false,"given":"S\u00f3nia","family":"Silva","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00005072-199603000-00001","article-title":"Neuropathology of Parkinson\u2019s disease","volume":"55","author":"Forno","year":"1996","journal-title":"J. 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