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Equine veterinary journal2000; 32(6); 497-504; doi: 10.2746/042516400777584730

Endotoxin and dietary amines may increase plasma 5-hydroxytryptamine in the horse.

Abstract: Uptake of 5-hydroxytryptamine (5-HT) into platelets is an important mechanism by which low plasma concentrations are maintained, and platelet activation may therefore result in significant release of this vasoconstrictor. The present study examined the kinetics of active uptake of radiolabelled [3H]5-HT by washed equine platelets in vitro, and investigated the effects on this process of 4 other naturally occurring monoamines which may be released from the caecum in conditions of carbohydrate overload. The release of [3H]5-HT by platelets was also studied, since platelet accumulation and activation has been associated with acute laminitis. Release of [3H]5-HT was measured in response to platelet activating factor (PAF), unlabelled 5-HT and the indirect activation of platelets by endotoxin in the presence of blood leucocytes. Km value for the uptake of 5-HT by equine platelets was 2.4 +/- 0.6 micromol/l and the Vmax was 8.3 +/- 0.6 pmol [3H]5-HT/10(7) platelets/min. The rate of uptake of 5 micromol/l [3H]5-HT was significantly decreased by the uptake inhibitors fluvoxamine and clomipramine. The 4 other monoamines examined all inhibited the uptake of [3H]5-HT in a noncompetitive manner, decreasing Vmax by between 17 and 82%. Incubation of platelets with LPS (0.1 mg/ml) in the absence of leucocytes did not result in significant release of [3H]5-HT; however, in the presence of leucocytes 3.8 +/- 1.7 pmol [3H]5-HT/10(7) platelets (mean +/- s.e.) were released. This release was significantly inhibited by parthenolide and WEB2086, but not by aspirin. This suggests that PAF from activated leucocytes was responsible for the 5-HT release. These data show that 5-HT uptake by equine platelets is a saturable process operating most efficiently at substrate concentrations in the low micromolar range. The noncompetitive inhibition of 5-HT uptake by other naturally occurring monoamines may result in increased plasma concentrations of 5-HT, as would its release by endotoxin. Such a rise in plasma 5-HT concentrations may contribute to selective vasoconstriction in the equine digital circulation.
Publication Date: 2000-11-28 PubMed ID: 11093623DOI: 10.2746/042516400777584730Google Scholar: Lookup
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  • Journal Article

Summary

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This scientific study focuses on the role of 5-hydroxytryptamine (5-HT) in horses. The researchers investigate how this compound, which constricts blood vessels, is absorbed and released by horse platelets under various conditions, particularly around dietary changes and exposure to endotoxin.

Study Explanation and Methodology

  • The research is centred around the uptake and release of 5-hydroxytryptamine (5-HT), known as serotonin in humans, by horse platelets. This compound is known to constrict blood vessels and platelets help to maintain low concentrations in the bloodstream.
  • The study also explored the impact of four other naturally occurring monoamines which are known to be released from the horse’s caecum when there’s an overload of carbohydrates in the diet. This was done to examine how these monoamines could affect the process related to 5-HT.
  • An important aspect of the study was the measurement and analysis of [3H]5-HT release by platelets. The researchers used this to understand the conditions under which the release happens, as it’s been associated with acute laminitis, a common disease in horses causing inflammation in the feet.

Key Findings

  • The researchers found that the uptake of 5-HT by horse platelets is a process that can reach saturation, working most efficiently with substrate concentrations in the low micromolar range.
  • The study concluded that the four monoamines they investigated all had an inhibitory effect on the uptake of [3H]5-HT. By inhibiting its absorption, this could lead to increased concentrations of 5-HT in the plasma.
  • A release of [3H]5-HT was observed when platelets were exposed to LPS (a form of endotoxin), especially when leucocytes (white blood cells) were present. This suggests that these leucocytes and their activation may play a key role in triggering the 5-HT release.
  • The increase in 5-HT plasma concentrations, brought about either by noncompetitive inhibition of uptake by other monoamines or by its release in response to endotoxins, could be a factor contributing to selective vasoconstriction in equine digital circulation – the blood circulation in the horse’s feet. This situation could be dangerous as it can lead to conditions like acute laminitis.

The findings of this study highlight how certain changes in diet and the presence of endotoxins could disrupt the balance of 5-HT in horses, affecting their health and potentially leading to diseases.

Cite This Article

APA
Bailey SR, Cunningham FM, Elliott J. (2000). Endotoxin and dietary amines may increase plasma 5-hydroxytryptamine in the horse. Equine Vet J, 32(6), 497-504. https://doi.org/10.2746/042516400777584730

Publication

ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 32
Issue: 6
Pages: 497-504

Researcher Affiliations

Bailey, S R
  • Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Cunningham, F M
    Elliott, J

      MeSH Terms

      • Amines / pharmacology
      • Animals
      • Aspirin / pharmacology
      • Azepines / pharmacology
      • Blood Platelets / metabolism
      • Cells, Cultured
      • Endotoxins / pharmacology
      • Horses / blood
      • Kinetics
      • Leukocytes / drug effects
      • Platelet Aggregation Inhibitors / pharmacology
      • Serotonin / blood
      • Triazoles / pharmacology

      Citations

      This article has been cited 2 times.
      1. Johnson PJ, Wiedmeyer CE, Messer NT, Ganjam VK. Medical implications of obesity in horses--lessons for human obesity. J Diabetes Sci Technol 2009 Jan;3(1):163-74.
        doi: 10.1177/193229680900300119pubmed: 20046661google scholar: lookup
      2. 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.
        doi: 10.1038/sj.bjp.0706431pubmed: 16230998google scholar: lookup