title: GLP-2 receptor expression in excitatory and inhibitory enteric neurons and its role in mouse duodenum contractility.
abstract: BACKGROUND
  Glucagon-like peptide 2 (GLP-2), a nutrient-responsive hormone, exerts various actions in the gastrointestinal tract that are mediated by a G-protein coupled receptor called GLP-2R. A little information is available on GLP-2R expression in enteric neurons and nothing on the interstitial cells of Cajal (ICC).
  
  
  METHODS
  We investigated presence and distribution of the GLP-2R in the mouse duodenum by immunohistochemistry and the potential motor effects of GLP-2 on the spontaneous and neurally evoked mechanical activity.
  
  
  RESULTS
  The GLP-2R was expressed by the myenteric and submucosal neurons. Labelling was also present in nerve varicosities within the circular muscular layer and at the deep muscular plexus (DMP). No immunoreactive nerve fiber was seen within the longitudinal muscle layer. The GLP-2R-positive neurons were either excitatory (SP- and choline-acetyltransferase-positive) or inhibitory (vasoactive intestinal polypeptide and nNOS-positive). The ICC, both at the myenteric plexus and at the DMP, never expressed GLP-2R but, especially those at the DMP, were surrounded by GLP-2R-positive nerve varicosities co-expressing either excitatory or inhibitory neurotransmitters. Quantitative analysis demonstrated a consistent prevalence of GLP-2R on the excitatory pathways. In agreement, the functional results showed that the administration of GLP-2 in vitro caused decrease of the spontaneous contractions mediated by nitric oxide release and reduction of the evoked cholinergic contractions.
  
  
  CONCLUSIONS
  The present findings indicate that the GLP-2R is expressed by inhibitory and excitatory neurons, the GLP-2 inhibits the muscle contractility likely decreasing cholinergic neurotransmission and increasing nitric oxide production, and this effect is possibly mediated by the ICC-DMP recruitment.
authors.affiliation: Department of Anatomy, Histology and Forensic Medicine, Section of Histology, University of Florence, Viale G. Pieraccini 6, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cinci
authors.forename: M S
authors.initials: MS
authors.lastname: Faussone-Pellegrini
authors.forename: A
authors.initials: A
authors.lastname: Rotondo
authors.forename: F
authors.initials: F
authors.lastname: Mulè
authors.forename: M G
authors.initials: MG
authors.lastname: Vannucchi
mesh_terms: D000818:Animals; D004386:Duodenum / Q000166:cytology / Q000294:innervation* / Q000502:physiology*; D017615:Enteric Nervous System / Q000166:cytology*; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism; D000067758:Glucagon-Like Peptide-2 Receptor; D006801:Humans; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism*
chemical_list: D053767:Glucagon-Like Peptide 2; D000067758:Glucagon-Like Peptide-2 Receptor; D018377:Neurotransmitter Agents; D018027:Receptors, Glucagon