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Neurogastroenterology and motility2017; 29(7); doi: 10.1111/nmo.13045

Localization of the 5-hydroxytryptamine 4 receptor in equine enteric neurons and extrinsic sensory fibers.

Abstract: Serotonin plays a pivotal role in regulating gut motility, visceral sensitivity, and fluid secretion via specific receptors. Among these receptors, 5-HT exerts a prominent control on gut motor function. Although the prokinetic effect exerted by 5-HT agonists is well known, the cellular sites of 5-HT expression remain poorly understood in large mammals, e.g., horses. In this study, we evaluated the distribution of 5-HT in 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-HT and a variety of neuronal markers. Myenteric and submucosal plexus 5-HT -immunoreactive (IR) neurons were quantified as relative percentage (mean±SD) to the total number of neurons counted. Furthermore, the density of 5-HT -IR nerve fibers was evaluated in the mucosa and tunica muscularis. Results: The 5-HT immunoreactivity 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-HT -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-HT in many enteric and extrinsic sensory neurons and nerve fibers provides solid morphological evidence of the cellular sites of 5-HT expression in horses. The evidence of SP-IR sensory neurons positive for 5-HT suggests its role in visceral sensitivity.
Publication Date: 2017-03-03 PubMed ID: 28256032DOI: 10.1111/nmo.13045Google Scholar: Lookup
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  • Journal Article

Summary

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The research article investigates the location and expression of the 5-HT serotonin receptor in the digestive system of horses and foals with a specific intestinal disorder. The findings provide new insights on serotonin’s role in gut regulation in large mammals.

Objective and Methodology

  • The purpose of this study was to determine the localization of the 5-hydroxytryptamines (5-HT) serotonin receptor in horses’ intestinal neurons and sensory fibers. This was prompted by existing knowledge of serotonin’s key role in controlling major gut functions but a lack of understanding about its exact site of expression in bigger mammals like horses.
  • The research was conducted on three healthy horses and two foals suffering from hereditary ileocolonic aganglionosis, a condition similar to human Hirschsprung’s disease characterized by missing nerve cells in the muscles of the colon.
  • Various sections of the horses’ intestines and spinal ganglia were harvested. The tissues were treated for immunohistochemistry using a 5-HT specific antibody coupled with different neuronal markers.
  • The researchers then analyzed the percentage of neurons showing 5-HT immunoreactivity within the total neurons counted. They also evaluated the density of nerve fibers expressing 5-HT in the mucous membrane and muscle layer of the intestine.

Key Findings

  • 5-HT immunoreactivity was observed in substantial percentages of the myenteric (inter-muscular) neurons, ranging between 28% in the descending colon and 63% in the ileum.
  • Similarly, the studied submucosal neurons also showed high levels of 5-HT immunoreactivity, between 54% in the ileum and 68% in the duodenum.
  • The researchers found co-expression of 5-HT immunoreactivity along with substance P-IR (an indicator of sensory neurons) in spinal ganglion neurons and extrinsic sensory fibers of the aganglionic foals.

Implications of the Study

  • The extensive presence of 5-HT in both enteric and extrinsic sensory neurons suggests that this specific type of serotonin receptor is predominantly present in large mammals’ gastrointestinal tract, specifically horses in this case.
  • The co-expression of 5-HT with SP-IR sensory neurons implies a possible role of serotonin in visceral sensitivity or the perception of internal body sensations.

Cite This Article

APA
Giancola F, Rambaldi AM, Bianco F, Iusco S, Romagnoli N, Tagliavia C, Bombardi C, Clavenzani P, De Giorgio R, Chiocchetti R. (2017). Localization of the 5-hydroxytryptamine 4 receptor in equine enteric neurons and extrinsic sensory fibers. Neurogastroenterol Motil, 29(7). https://doi.org/10.1111/nmo.13045

Publication

ISSN: 1365-2982
NlmUniqueID: 9432572
Country: England
Language: English
Volume: 29
Issue: 7

Researcher Affiliations

Giancola, F
  • 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.
Rambaldi, A M
  • Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
Bianco, F
  • 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.
Iusco, S
  • Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
Romagnoli, N
  • Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
Tagliavia, C
  • Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
Bombardi, C
  • Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
Clavenzani, P
  • Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
De Giorgio, R
  • Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Chiocchetti, R
  • Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.

MeSH Terms

  • Animals
  • Enteric Nervous System / chemistry
  • Enteric Nervous System / metabolism
  • Gastrointestinal Tract / chemistry
  • Gastrointestinal Tract / metabolism
  • Horses
  • Male
  • Myenteric Plexus / chemistry
  • Myenteric Plexus / metabolism
  • Receptors, Serotonin, 5-HT4 / analysis
  • Receptors, Serotonin, 5-HT4 / metabolism
  • Sensory Receptor Cells / chemistry
  • Sensory Receptor Cells / metabolism

Citations

This article has been cited 6 times.
  1. Diana A, Freccero F, Giancola F, Linta N, Pietra M, Luca V, Salamanca G, Cipone M, Chiocchetti R. Ex vivo ultrasonographic and histological morphometry of small intestinal wall layers in horses. Vet Radiol Ultrasound 2022 May;63(3):353-363.
    doi: 10.1111/vru.13059pubmed: 35171532google scholar: lookup
  2. Chiocchetti R, Galiazzo G, Giancola F, Tagliavia C, Bernardini C, Forni M, Pietra M. Localization of the Serotonin Transporter in the Dog Intestine and Comparison to the Rat and Human Intestines. Front Vet Sci 2021;8:802479.
    doi: 10.3389/fvets.2021.802479pubmed: 35071391google scholar: lookup
  3. Derkinderen P, Cossais F, de Guilhem de Lataillade A, Leclair-Visonneau L, Neunlist M, Paillusson S, De Giorgio R. Gastrointestinal mucosal biopsies in Parkinson's disease: beyond alpha-synuclein detection. J Neural Transm (Vienna) 2022 Sep;129(9):1095-1103.
    doi: 10.1007/s00702-021-02445-6pubmed: 34816335google scholar: lookup
  4. Galiazzo G, De Silva M, Giancola F, Rinnovati R, Peli A, Chiocchetti R. Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia. Equine Vet J 2021 Aug 21;54(4):788-98.
    doi: 10.1111/evj.13499pubmed: 34418142google scholar: lookup
  5. Galiazzo G, Giancola F, Stanzani A, Fracassi F, Bernardini C, Forni M, Pietra M, Chiocchetti R. Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract. Histochem Cell Biol 2018 Aug;150(2):187-205.
    doi: 10.1007/s00418-018-1684-7pubmed: 29882158google scholar: lookup
  6. Tang X, Huang Y, Jiang T, Wu J, Wang K, Wu W. Pathophysiological mechanisms, diagnostic innovations, and multimodal therapeutic strategies for slow transit constipation. BMC Gastroenterol 2025 Nov 17;25(1):810.
    doi: 10.1186/s12876-025-04387-9pubmed: 41249937google scholar: lookup