Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure.
Abstract: In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT(7) receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively. 5-HT(7) immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT(7) immunoreactivity. The selective 5-HT(7) receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently. Our in vitro experiments suggest an involvement of the 5-HT(7) receptor subtype in contractility of equine intestine. While the 5-HT(7) receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT(7) receptor ligand SB-269970, suggesting it exerting inverse agonist properties.
Publication Date: 2009-04-11 PubMed ID: 19364615PubMed Central: PMC2713387DOI: 10.1016/j.rvsc.2009.03.009Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Intramural
- Research Support
- Non-U.S. Gov't
Summary
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This study focuses on the role and location of 5-HT7 receptors in the gastrointestinal (GI) tract of horses with the aim of providing insights for developing efficient medication for equine GI disorders. The paper details a series of experiments studying the expression of 5-HT7 receptors in the duodenum, ileum, and pelvic flexure of horses, and their role in modulating intestinal contractility.
5-HT7 Receptors and GI Tract Motility
- 5-Hydroxytryptamine receptors (5-HT), including the 5-HT7 subtype, are known to influence the motility of the GI tract, making them viable targets for medication intended to treat functional bowel disorders in horses.
- By studying the expression of these receptors in different parts of the equine intestine, the researchers attempt to further enhance knowledge about the function and importance of the 5-HT7 receptor in the GI tract.
Experimental Methodology and Results
- The researchers used immunofluorescence and organ bath experiments to study the expression of 5-HT7 receptors and the impact they may have on intestinal contractility.
- They found evidence of 5-HT7 immunoreactivity or protein production in both smooth muscle layers (the circular and longitudinal ones), and within the myenteric plexus, an area containing nerves that control GI tract peristalsis.
- Interstitial cells of Cajal (ICC), which coordinate smooth muscle contractions in the GI tract, showed a staining pattern very similar to that of the 5-HT7 receptor.
- The study found that SB-269970, a selective 5-HT7 receptor antagonist, concentration-dependently increased the amplitude of contractions in spontaneously contracting ileum specimens and electrically stimulated pelvic flexure specimens, hinting at the potential regulatory role of the 5-HT7 receptor for equine intestine contraction.
Implications and Interpretation
- Conventionally, 5-HT7 receptors are thought to be constitutively active and inhibit smooth muscle contractility.
- However, in this study, the increase in intestinal contractions upon treatment with the 5-HT7 receptor ligand, SB-269970, indicates an inverse agonist property – suggesting that they might actually boost contractility under certain conditions.
- This enhanced understanding of the 5-HT7 receptor’s function could lead to more effective treatments for equine GI disorders, with the potential for drug development to boost or inhibit the receptor’s activity.
Cite This Article
APA
Prause AS, Stoffel MH, Portier CJ, Mevissen M.
(2009).
Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure.
Res Vet Sci, 87(2), 292-299.
https://doi.org/10.1016/j.rvsc.2009.03.009 Publication
Researcher Affiliations
- Division Veterinary Pharmacology and Toxicology, University of Berne, 3012 Berne, Switzerland.
MeSH Terms
- Animals
- Biomarkers / analysis
- Duodenum / physiology
- Gastrointestinal Diseases / epidemiology
- Gastrointestinal Diseases / veterinary
- Horse Diseases / epidemiology
- Horse Diseases / mortality
- Horse Diseases / physiopathology
- Horses
- Ileum / physiology
- Muscle Contraction / drug effects
- Muscle, Smooth / physiology
- Pelvic Floor / physiology
- Phenols / pharmacology
- Receptors, Serotonin / physiology
- Risk Factors
- Sulfonamides / pharmacology
Grant Funding
- Z01 ES048002-20 / Intramural NIH HHS
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Citations
This article has been cited 4 times.- Xu Z, Chen JJ, Mei Q, Li Y, Xu J. Expression of 5-hydroxytryptamine 7 receptor in intestinal mucosa correlates with the degree of intestinal inflammation in Crohn's disease.. BMC Gastroenterol 2022 Nov 15;22(1):457.
- Beder NA, Mourad AA, Aly MA. Ultrasonographic evaluation of the effects of the administration of neostigmine and metoclopramide on duodenal, cecal, and colonic contractility in Arabian horses: A comparative study.. Vet World 2020 Nov;13(11):2447-2451.
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