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British journal of pharmacology2005; 147(1); 23-35; doi: 10.1038/sj.bjp.0706431

Contractile effects of 5-hydroxytryptamine and 5-carboxamidotryptamine in the equine jejunum.

Abstract: The use of human prokinetic drugs in colic horses leads to inconsistent results. This might be related to differences in gastrointestinal receptor populations. The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the equine mid-jejunum were therefore studied. Longitudinal muscle preparations were set up for isotonic measurement. 5-HT induced tonic contractions with superimposed phasic activity; these responses were not influenced by tetrodotoxin and atropine, suggesting a non-neurogenic, non-cholinergic pathway. The 5-HT receptor antagonists GR 127935 (5-HT(1B,D)), ketanserin (5-HT(2A)), SB 204741 (5-HT(2B)), RS 102221 (5-HT(2C)), granisetron (5-HT(3)), GR 113808 (5-HT(4)) and SB 269970 (5-HT(7)) had no influence on the 5-HT-induced response; the 5-HT(1A) receptor antagonists NAN 190 (pK(b)=8.13+/-0.06) and WAY 100635 (pK(b)=8.69+/-0.07), and the 5-HT(1,2,5,6,7) receptor antagonist methysergide concentration-dependently inhibited the 5-HT-induced contractile response. The 5-HT(1,7) receptor agonist 5-carboxamidotryptamine (5-CT) induced a contractile response similar to that of 5-HT; its effect was not influenced by tetrodotoxin and atropine, and SB 269970, but antagonised by WAY 100635. 8-OHDPAT, buspiron and flesinoxan, which are active at rat and human 5-HT(1A) receptors, had no contractile influence. These results suggest that the contractile effect of 5-HT in equine jejunal longitudinal muscle is due to interaction with muscular 5-HT receptors, which cannot be characterised between the actually known classes of 5-HT receptors.
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Publication Date: 2005-10-19 PubMed ID: 16230998PubMed Central: PMC1615837DOI: 10.1038/sj.bjp.0706431Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines how serotonin (5-hydroxytryptamine or 5-HT) affects muscle contractions in horse intestines, namely in the jejunum. The study specifically focuses on understanding why common human prokinetic drugs, which boost gastrointestinal activity, show varied effects when used in horses.

Research Methodology

  • The research involved studying the effects of 5-HT on the mid-section of the horse jejunum. The jejunum is part of the small intestine in the equine digestive system.
  • Muscle preparations were created for isotonic measurement. This process allows the measurement of muscle contraction while keeping the pressure constant.
  • To trigger effects, the researchers exposed the muscle preparations to 5-HT. This induced both tonic contractions, which are sustained muscle contractions, and phasic activity, which involves rhythmic, repeated contractions and relaxations.
  • The researchers also observed the effects of various receptor antagonists on the 5-HT responses. These antagonists include GR 127935, ketanserin, SB 204741, RS 102221, granisetron, GR 113808, SB 269970, NAN 190, WAY 100635, and methysergide. They work by blocking specific receptors that interface with 5-HT, effectively reducing or inhibiting its effects.

Results

  • The researchers found that 5-HT-induced responses were not influenced by tetrodotoxin and atropine, suggesting that the action pathway was not connected to the nerve cells (non-neurogenic) or reliant on acetylcholine (non-cholinergic). Tetrodotoxin is a neurotoxin that inhibits nerve signals while atropine is often used to control muscle activities.
  • Most of the receptor antagonists had no influence on the 5-HT-induced response, except for the 5-HT(1A) receptor antagonists NAN 190 and WAY 100635, and the 5-HT(1,2,5,6,7) receptor antagonist methysergide, which inhibited the 5-HT-induced contractile response in a concentration-dependent manner.
  • Similarly, the 5-HT(1,7) receptor agonist 5-carboxamidotryptamine (5-CT), which activates some of the same receptors as 5-HT, triggered a contractile response similar to that of 5-HT, and was not influenced by tetrodotoxin, atropine or SB 269970 but was inhibited by WAY 100635.
  • Some substances that act on rat and human 5-HT(1A) receptors, like 8-OHDPAT, buspiron and flesinoxan, had no impact on the muscle contractions in this study.

Conclusion

The study concludes that the contractile effect of 5-HT in the equine jejunum’s longitudinal muscle mainly results from interaction with muscular 5-HT receptors. The research did not manage to definitively classify these receptors among the currently known classes of 5-HT receptors. Therefore, these results could provide a step towards understanding why human prokinetic drugs have varied effects in horses and might lead to further investigation on the topic in an effort to improve treatment for equine digestive disorders, such as colic.

Cite This Article

APA
Delesalle C, Deprez P, Schuurkes JA, Lefebvre RA. (2005). Contractile effects of 5-hydroxytryptamine and 5-carboxamidotryptamine in the equine jejunum. Br J Pharmacol, 147(1), 23-35. https://doi.org/10.1038/sj.bjp.0706431

Publication

British journal of pharmacology
ISSN: 0007-1188
NlmUniqueID: 7502536
Country: England
Language: English
Volume: 147
Issue: 1
Pages: 23-35

Researcher Affiliations

Delesalle, Cathérine
  • Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. Catherine.Delesalle@UGent.be
Deprez, Piet
    Schuurkes, Jan A J
      Lefebvre, Romain A

        MeSH Terms

        • Animals
        • Dose-Response Relationship, Drug
        • Horses
        • Jejunum / physiology
        • Muscle Contraction / drug effects
        • Serotonin / analogs & derivatives
        • Serotonin / pharmacology
        • Serotonin Agents / pharmacology
        • Serotonin Receptor Agonists / pharmacology

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        Citations

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        2. Alberghina D, Giannetto C, Piccione G. Peripheral serotoninergic response to physical exercise in athletic horses. J Vet Sci 2010 Dec;11(4):285-9.
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        3. 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.
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