title: Toll-like receptors 2 and 4 modulate the contractile response induced by serotonin in mouse ileum: analysis of the serotonin receptors involved.
abstract: BACKGROUND
  Microbiota through toll-like receptors (TLR) may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in the spontaneous contractions and serotonin (5-HT)-induced motor response in mouse ileum, and the 5-HT receptors involved.
  
  
  METHODS
  Muscle contractility studies to evaluate the spontaneous intestinal motility and the response to 5-HT were performed in the ileum from wild type (WT), TLR2(-/-), TLR4(-/-), and TLR2/4 double knockout (DKO) mice. 5-HT receptor expression was determined by real-time PCR.
  
  
  RESULTS
  The amplitude of spontaneous contractions in ileum was higher in TLR2(-/-), TLR4(-/-), and TLR2/4 DKO mice with respect to WT. 5-HT evoked concentration-dependent contractile responses in the ileum from TLR2(-/-) and TLR4(-/-) mice similar to WT. However, in ileum from TLR2/4 DKO, 5-HT did not induce any contractile response. Expression of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT3 receptors resulted increased in ileum from TLR4(-/-) and TLR2/4 DKO. Expression of the 5-HT4 receptor was diminished in TLR2(-/-) and TLR2/4 DKO. High levels of 5-HT7 receptor expression were found in TLR2/4 DKO but not in TLR2(-/-) or TLR4(-/-). In WT and TLR4(-/-), 5-HT2, 5-HT3, 5-HT4, and 5-HT7 receptor antagonists reduced the contractile response evoked by 5-HT. In TLR2(-/-) mice, 5-HT4 antagonist did not reduce the 5-HT response. In TLR2/4 DKO mice, only 5-HT4 and 5-HT7 receptor antagonists reduced the relaxing response induced by 5-HT.
  
  
  CONCLUSIONS
  TLR2 and TLR4 signaling may modulate the spontaneous contractions and the serotonin contractile response by acting on 5-HT2, 5-HT3, 5-HT4, and 5-HT7 receptors.
authors.affiliation: Departamento de Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Forcén
authors.affiliation: Departamento de Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Latorre
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pardo
authors.affiliation: Departamento de Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Alcalde
authors.affiliation: Departamento de Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Murillo
authors.affiliation: Departamento de Farmacología y Fisiología, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Grasa
mesh_terms: D000818:Animals; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D012701:Serotonin
keywords: TLR2; TLR4; immune response; intestinal motility; microbiota; serotonin receptors