TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors; 35681486

Layunta, E. (Universidad de Zaragoza) ; Forcén, R. ; Grasa López, L. (Universidad de Zaragoza)

Resumen: 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-/- and TLR4-/- 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) a3ß4 antagonist) and a-bungarotoxin (a nAChR a7 antagonist). In TLR2-/- mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4-/- mice, the contractions induced by ACh were reduced by a-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and a3 receptors were diminished in the ileum from TLR2-/- and TLR4-/- with respect to WT mice. However, the levels of mRNA and protein of ß4 were diminished only in TLR4-/- but not in TLR2-/- 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 a3ß4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic a3ß4 and a7 ACh receptors.

Idioma: Inglés

DOI: 10.3390/cells11111791

Año: 2022

Publicado en: Cells 11, 11 (2022), 1791 [13 pp]
ISSN: 2073-4409

Factor impacto JCR: 6.0 (2022)

Categ. JCR: CELL BIOLOGY rank: 60 / 191 = 0.314 (2022) - Q2 - T1

Factor impacto CITESCORE: 9.0 - Medicine (Q1)

Factor impacto SCIMAGO: 1.537 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B61

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)