{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:40Z","timestamp":1787027800586,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010067","name":"Gobierno de Arag\u00f3n","doi-asserted-by":"publisher","award":["B61\/2016"],"award-info":[{"award-number":["B61\/2016"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by intestinal dysmotility. Changes in intestinal microbiota (dysbiosis) can lead to alterations in neuro-muscular functions in the gut. Toll-like receptors (TLRs) 2 and 4 recognize intestinal bacteria and are involved in the motor response induced by gastrointestinal (GI) neurotransmitters. Acetylcholine (ACh) is a well-known neurotransmitter involved in the regulation of GI motility. This study aimed to evaluate the role of TLR2 and TLR4 in the intestinal motor-response induced by ACh in the mouse ileum, as well as the expression and function of the muscarinic and nicotinic ACh receptors. Muscle contractility studies showed that the contractions induced by ACh were significantly lower in TLR2\u2212\/\u2212 and TLR4\u2212\/\u2212 with respect to WT mice. In WT mice, the contractions induced by ACh were reduced in the presence of AF-DX AF-DX 116 (a muscarinic ACh receptor (mAChR) M2 antagonist), 4-DAMP (a mAChR M3 antagonist), mecamylamine (a nicotinic AChR receptor (nAChR) \u03b13\u03b24 antagonist) and \u03b1-bungarotoxin (a nAChR \u03b17 antagonist). In TLR2\u2212\/\u2212 mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4\u2212\/\u2212 mice, the contractions induced by ACh were reduced by \u03b1-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and \u03b13 receptors were diminished in the ileum from TLR2\u2212\/\u2212 and TLR4\u2212\/\u2212 with respect to WT mice. However, the levels of mRNA and protein of \u03b24 were diminished only in TLR4\u2212\/\u2212 but not in TLR2\u2212\/\u2212 mice. In conclusion, our results show that TLR2 and TLR4 modulates the motor responses to ACh in the mouse ileum. TLR2 acts on muscarinic M2 and M3 and nicotinic \u03b13\u03b24 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic \u03b13\u03b24 and \u03b17 ACh receptors.<\/jats:p>","DOI":"10.3390\/cells11111791","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T10:05:14Z","timestamp":1653905114000},"page":"1791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5573-6144","authenticated-orcid":false,"given":"Elena","family":"Layunta","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9C, 41390 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Forc\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Fisiolog\u00eda y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5306-9365","authenticated-orcid":false,"given":"Laura","family":"Grasa","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Fisiolog\u00eda y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n\u2014IA2\u2014(Universidad de Zaragoza-CITA), 50013 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16014","DOI":"10.1038\/nrdp.2016.14","article-title":"Irritable bowel syndrome","volume":"2","author":"Enck","year":"2016","journal-title":"Nat. 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