TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors
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 involve...
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/11/1791 |
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| author | Elena Layunta Raquel Forcén Laura Grasa |
| author_facet | Elena Layunta Raquel Forcén Laura Grasa |
| author_sort | Elena Layunta |
| collection | DOAJ |
| description | 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<sup>−/−</sup> and TLR4<sup>−/−</sup> 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) α3β4 antagonist) and α-bungarotoxin (a nAChR α7 antagonist). In TLR2<sup>−/−</sup> mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4<sup>−/−</sup> mice, the contractions induced by ACh were reduced by α-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and α3 receptors were diminished in the ileum from TLR2<sup>−/−</sup> and TLR4<sup>−/−</sup> with respect to WT mice. However, the levels of mRNA and protein of β4 were diminished only in TLR4<sup>−/−</sup> but not in TLR2<sup>−/−</sup> 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 α3β4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic α3β4 and α7 ACh receptors. |
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| language | English |
| last_indexed | 2024-03-10T01:25:09Z |
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| spelling | doaj.art-c619f871373647f5b2da163e8474d4c02023-11-23T13:52:50ZengMDPI AGCells2073-44092022-05-011111179110.3390/cells11111791TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic ReceptorsElena Layunta0Raquel Forcén1Laura Grasa2Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9C, 41390 Gothenburg, SwedenDepartamento de Farmacología, Fisiología y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, SpainDepartamento de Farmacología, Fisiología y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, SpainIrritable 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<sup>−/−</sup> and TLR4<sup>−/−</sup> 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) α3β4 antagonist) and α-bungarotoxin (a nAChR α7 antagonist). In TLR2<sup>−/−</sup> mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4<sup>−/−</sup> mice, the contractions induced by ACh were reduced by α-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and α3 receptors were diminished in the ileum from TLR2<sup>−/−</sup> and TLR4<sup>−/−</sup> with respect to WT mice. However, the levels of mRNA and protein of β4 were diminished only in TLR4<sup>−/−</sup> but not in TLR2<sup>−/−</sup> 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 α3β4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic α3β4 and α7 ACh receptors.https://www.mdpi.com/2073-4409/11/11/1791microbiotatoll-like receptorsintestinal motilitynicotinic receptorsmuscarinic receptors |
| spellingShingle | Elena Layunta Raquel Forcén Laura Grasa TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors Cells microbiota toll-like receptors intestinal motility nicotinic receptors muscarinic receptors |
| title | TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors |
| title_full | TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors |
| title_fullStr | TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors |
| title_full_unstemmed | TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors |
| title_short | TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors |
| title_sort | tlr2 and tlr4 modulate mouse ileal motility by the interaction with muscarinic and nicotinic receptors |
| topic | microbiota toll-like receptors intestinal motility nicotinic receptors muscarinic receptors |
| url | https://www.mdpi.com/2073-4409/11/11/1791 |
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