Uptake of 5-hydroxytryptamine by equine digital vein endothelial cells: inhibition by amines found in the equine caecum.
Abstract: 5-hydroxytryptamine (5-HT; serotonin) is a potent vasoconstrictor of equine digital blood vessels and has been implicated in the pathogenesis of acute laminitis. Objective: The aims of this study were firstly to examine whether cells of the digital blood vessel wall exhibited an active uptake mechanism for 5-HT and to characterise its efficiency; and secondly, to study the potential inhibitory effect on this process of other amines, produced in the equine caecum. Methods: Confluent monolayers of equine digital vein endothelial cells (EDVEC) and equine digital vein smooth muscle cells (EDVSMC) were incubated with [3H]5-HT (0.1-250 micromol/l) and the total and active uptake calculated. Equine pulmonary vein endothelial cells (EPVEC) were used as a positive control. Results: Both EDVEC and EDVSMC showed uptake of [3H]5-HT by nonfaci litated diffusion; however, only EDVEC showed evidence of saturable facilitated uptake mechanism, with a Km of 41.6 +/- 9.3 micromol/l, which was significantly higher than that of EPVEC (9.9 +/- 2.1 micromol/l). All 6 caecally-derived amines examined (tyramine, spermine, isoamylamine, tryptamine, phenylethylamine and isobutylamine) inhibited the total uptake of [3H]5-HT in a concentration-dependent manner, tyramine having the lowest IC50 (3.7 x 10(-6) mol/l). Conclusions: These data suggest that facilitated uptake into the endothelium could play a role in moderating the vasoconstrictor response to 5-HT in the equine digital circulation. Conclusions: The vasoconstrictor action of 5-HT could be potentiated by gut-derived amines, providing a feasible link between GI disturbances and the pathophysiology of laminits.
Publication Date: 2003-03-18 PubMed ID: 12638793DOI: 10.2746/042516403776114171Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research work is examining the uptake of a chemical named 5-hydroxytryptamine by cells of horse’s digital blood vessel. It also studies the impact of other amines produced in the horse’s caecum on this process. The insights point towards a potential connection between gastrointestinal disturbances and horse foot disease (laminitis).
Research Objectives
- The core objective of the study was to understand the interaction between 5-hydroxytryptamine, also known as serotonin, and cells in the equine digital blood vessel system. Serotonin is identified as a significant vasoconstrictor in these digital blood vessels and suspected to be connected to acute laminitis, a debilitating condition in horses affecting their hooves.
- The researchers sought to confirm the existence of an active uptake mechanism for serotonin in these cells, and then characterize its efficiency.
- The secondary objective was to study the potential impacts of other amines (organic compounds derived from ammonia) produced in the equine caecum on this active uptake process. The caecum is part of the horse’s digestive tract where fermentation of plant fiber occurs.
Methodology
- The researchers nurtured two types of cells from the equine digital blood vessel: the endothelial cells, which line the interior of the vessels, and the smooth muscle cells, which form part of the vessel wall structure. They then introduced radiolabelled serotonin into these cultures.
- As a comparative control, they used equine pulmonary vein endothelial cells, which are known to uptake serotonin.
Findings
- Results showed that both endothelial and smooth muscle cells take in serotonin through nonfacilitated diffusion, a natural process not requiring any energy consumption. But only endothelial cells demonstrated facilitated uptake – a more active process which helps in transporting certain molecules across cell membranes.
- The efficiency of this active uptake in endothelial cells was significantly less than that of the control cells. This implies a potentially weaker regulation of serotonin-induced vasoconstriction.
- All amines from the caecum were found to inhibit serotonin uptake in a concentration-dependent way. This suggests that they can potentially enhance the vasoconstrictor action of serotonin.
Conclusions
- The findings suggest that the mechanism of facilitated uptake into the endothelium could help moderate the vasoconstrictive responses to serotonin in the horse’s digital circulation.
- The study supports the theory that serotonin’s vasoconstrictive action could be intensified by certain gut-derived amines. This connection could provide a plausible link between gastrointestinal disturbances and the onset and severity of laminitis in horses.
Cite This Article
APA
Bailey SR, Wheeler-Jones C, Elliott J.
(2003).
Uptake of 5-hydroxytryptamine by equine digital vein endothelial cells: inhibition by amines found in the equine caecum.
Equine Vet J, 35(2), 164-169.
https://doi.org/10.2746/042516403776114171 Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 OTU, UK.
MeSH Terms
- Amines / metabolism
- Amines / pharmacology
- Animals
- Cecum / metabolism
- Cells, Cultured
- Dose-Response Relationship, Drug
- Endothelium, Vascular / cytology
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / metabolism
- Foot Diseases / etiology
- Foot Diseases / veterinary
- Free Radical Scavengers
- Hoof and Claw / blood supply
- Horse Diseases / blood
- Horse Diseases / etiology
- Horses
- Muscle, Smooth, Vascular / cytology
- Muscle, Smooth, Vascular / metabolism
- Serotonin / metabolism
- Serotonin Antagonists / pharmacology
- Tritium
- Vasoconstriction / drug effects
Citations
This article has been cited 4 times.- Andrews PW, Bosyj C, Brenton L, Green L, Gasser PJ, Lowry CA, Pickel VM. All the brain's a stage for serotonin: the forgotten story of serotonin diffusion across cell membranes.. Proc Biol Sci 2022 Nov 9;289(1986):20221565.
- Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J. The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro.. Inflamm Res 2014 Aug;63(8):637-47.
- Gauff F, Patan-Zugaj B, Licka TF. Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit.. Equine Vet J 2013 Sep;45(5):613-8.
- Brooks AC, Menzies-Gow N, Bailey SR, Cunningham FM, Elliott J. Endotoxin-induced HIF-1alpha stabilisation in equine endothelial cells: synergistic action with hypoxia.. Inflamm Res 2010 Sep;59(9):689-98.
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