title: Localization of the 5-hydroxytryptamine 4 receptor in equine enteric neurons and extrinsic sensory fibers.
abstract: BACKGROUND
  Serotonin plays a pivotal role in regulating gut motility, visceral sensitivity, and fluid secretion via specific receptors. Among these receptors, 5-HT4exerts a prominent control on gut motor function. Although the prokinetic effect exerted by 5-HT4agonists is well known, the cellular sites of 5-HT4expression remain poorly understood in large mammals, e.g., horses. In this study, we evaluated the distribution of 5-HT4in the horse intestine and in foals with enteric aganglionosis, reminiscent of human Hirschsprung's disease.
  
  
  METHODS
  The intestine and spinal ganglia were obtained from three healthy horses and two foals with hereditary ileocolonic aganglionosis. Tissues were processed for immunohistochemistry using a specific antibody to 5-HT4and a variety of neuronal markers. Myenteric and submucosal plexus 5-HT4-immunoreactive (IR) neurons were quantified as relative percentage (mean±SD) to the total number of neurons counted. Furthermore, the density of 5-HT4-IR nerve fibers was evaluated in the mucosa and tunica muscularis.
  
  
  RESULTS
  The 5-HT4immunoreactivity was localized to large percentages of myenteric neurons ranging from 28±9% (descending colon) to 63±19% (ileum), and submucosal neurons ranging from 54±6% (ileum) to 68±14% (duodenum). The 5-HT4-immunoreactivity was co-expressed by some substance P-IR (SP-IR) spinal ganglion neurons and extrinsic sensory fibers of aganglionic foals.
  
  
  CONCLUSIONS
  The presence of 5-HT4in many enteric and extrinsic sensory neurons and nerve fibers provides solid morphological evidence of the cellular sites of 5-HT4expression in horses. The evidence of SP-IR sensory neurons positive for 5-HT4suggests its role in visceral sensitivity.
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.|Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Giancola
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Rambaldi
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.|Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bianco
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Iusco
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Romagnoli
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tagliavia
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bombardi
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Clavenzani
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Giorgio
authors.affiliation: Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
authors.forename: R
authors.identifier: http://orcid.org/0000-0003-4448-6199
authors.initials: R
authors.lastname: Chiocchetti
mesh_terms: D000818:Animals; D017615:Enteric Nervous System / Q000737:chemistry* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000378:metabolism; D006736:Horses; D008297:Male; D009197:Myenteric Plexus / Q000737:chemistry / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4 / Q000032:analysis* / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000737:chemistry* / Q000378:metabolism
chemical_list: D044422:Receptors, Serotonin, 5-HT4
keywords: 5-hydroxytryptamine receptor type 4; enteric nervous system; lethal white foal syndrome; prokinetic; serotonin