5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist.
Abstract: The effects of 5-hydroxytryptamine (5-HT), HTF 919, a new 5-HT(4) agonist, and the antagonists SB 203-186 (5-HT(4)) and tropisetron (5-HT(3)) on intestinal motility were tested in vitro on isolated preparations of horse ileum and pelvic flexure. Concentration-response curves were created by cumulative application of the agonists with or without preincubation of the antagonists. The 5-HT preparation induced a concentration-dependent contraction in equine ileum and pelvic flexure. The results indicate that 5-HT receptors are present in all parts of equine intestine investigated in this study. Tropisetron was found to act as a noncompetitive antagonist in all locations of the equine intestine. SB 203-106 was confirmed as an antagonist to 5-HT in the equine ileum circular muscle, in pelvic flexure circular and longitudinal muscle. Nevertheless, a discernible increase of smooth muscle contractions caused by HTF 919 could only be observed in pelvic flexure. In accordance with an earlier study in the guinea pig, in the equine gut HTF 919 acted as a partial agonist for the 5-HT(4) receptor with an affinity constant in the nanomolar range. It is concluded that 5-HT receptors, and especially their subtypes, may represent a promising target for the treatment and prevention of gastrointestinal (GI) motility disorders in horses.
Publication Date: 2002-03-05 PubMed ID: 11874527DOI: 10.1046/j.1365-2885.2002.00380.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates the impact of serotonin (5-hydroxytryptamine or 5-HT) and a new serotonin receptor agonist, HTF 919, on the movement of horse intestine tissue in lab settings, specifically the ileum and pelvic flexure.
Study Design and Methods
- Isolation and preparation of horse’s ileum and pelvic flexure tissues for in vitro testing
- Treatment of these tissues with 5-HT, HTF 919 (a new serotonin 4 [5-HT(4)] receptor agonist), and antagonists SB 203-186 (which blocks the 5-HT(4) receptor) and tropisetron (which inhibits the 5-HT(3) receptor)
- Establishment of concentration-response curves by progressively adding the agonists with or without prior treatment with the antagonists
Key Findings
The primary findings of their research are:
- 5-HT instigates contraction in equine ileum and pelvic flexure in a concentration-dependent manner, which demonstrates the existence of 5-HT receptors in all parts of horse intestines studied
- An antagonist at the 5-HT(3) receptor, tropisetron, was identified as a noncompetitive antagonist in all areas of horse intestines
- SB 203-106 confirmed as a 5-HT antagonist in the circular muscle of the equine ileum, as well as in the circular and longitudinal muscle of the pelvic flexure
- HTF 919 only visible raised smooth muscle contractions in the pelvic flexure
- HTF 919 acts as a partial 5-HT(4) receptor agonist in the horse intestine, similar to its behaviours in guinea pigs in previous studies, with an affinity constant in the nanomolar range
Conclusions and Implications
Based on these results, the researchers suggest that the 5-HT receptors and their subtypes within the horse’s gastrointestinal system may be potential targets for the treatment and prevention of motility disorders. This is noteworthy as variations in the contractions of these muscles can cause a range of digestive issues in horses. An effective treatment could significantly improve the health and well-being of affected animals.
Cite This Article
APA
Weiss R, Abel D, Scholtysik G, Straub R, Mevissen M.
(2002).
5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist.
J Vet Pharmacol Ther, 25(1), 49-58.
https://doi.org/10.1046/j.1365-2885.2002.00380.x Publication
Researcher Affiliations
- Institute of Veterinary Pharmacology, University of Bern, CH-3012 Bern, Switzerland.
MeSH Terms
- Animals
- Dose-Response Relationship, Drug
- Female
- Gastrointestinal Motility
- Horses / physiology
- Ileum / drug effects
- Ileum / physiology
- Indoles / administration & dosage
- Indoles / pharmacology
- Male
- Muscle Contraction / drug effects
- Muscle Contraction / physiology
- Muscle, Smooth / drug effects
- Muscle, Smooth / physiology
- Pelvic Floor / physiology
- Piperidines / administration & dosage
- Piperidines / pharmacology
- Serotonin / administration & dosage
- Serotonin / pharmacology
- Serotonin Antagonists / administration & dosage
- Serotonin Antagonists / pharmacology
- Serotonin Receptor Agonists / administration & dosage
- Serotonin Receptor Agonists / pharmacology
- Tropisetron
Citations
This article has been cited 5 times.- Laus F, Fratini M, Paggi E, Faillace V, Spaterna A, Tesei B, Fettucciari K, Bassotti G. Effects of Single-Dose Prucalopride on Intestinal Hypomotility in Horses: Preliminary Observations. Sci Rep 2017 Jan 27;7:41526.
- Alberghina D, Giannetto C, Piccione G. Peripheral serotoninergic response to physical exercise in athletic horses. J Vet Sci 2010 Dec;11(4):285-9.
- Okamura K, Sasaki N, Kikuchi T, Murata A, Lee I, Yamada H, Inokuma H. Effects of mosapride on motility of the small intestine and caecum in normal horses after jejunocaecostomy. J Vet Sci 2009 Jun;10(2):157-60.
- Prause AS, Stoffel MH, Portier CJ, Mevissen M. Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure. Res Vet Sci 2009 Oct;87(2):292-9.
- Delesalle C, Deprez P, Schuurkes JA, Lefebvre RA. Contractile effects of 5-hydroxytryptamine and 5-carboxamidotryptamine in the equine jejunum. Br J Pharmacol 2006 Jan;147(1):23-35.
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