Endotoxin and dietary amines may increase plasma 5-hydroxytryptamine in the horse.
Authors: Bailey S R, Cunningham F M, Elliott J
Journal: Equine veterinary journal
Summary
# Editorial Summary Bailey and colleagues investigated how serotonin (5-hydroxytryptamine; 5-HT) is regulated in equine blood, specifically examining platelet uptake mechanisms and factors that might impair this critical clearance pathway. Using radiolabelled serotonin in vitro, the researchers characterised the kinetics of platelet uptake (Km 2.4 µmol/l, Vmax 8.3 pmol/10⁷ platelets/min) and demonstrated that four naturally occurring monoamines—which accumulate in the caecum during carbohydrate overload—all noncompetitively inhibited this uptake process, reducing maximum uptake velocity by 17–82%. Critically, when lipopolysaccharide (endotoxin) was incubated with platelets and blood leucocytes together, approximately 3.8 pmol serotonin per 10⁷ platelets was released, an effect mediated by platelet-activating factor from activated leucocytes rather than direct endotoxin action. These findings suggest that both dietary amines (from colonic dysbiosis) and endotoxaemia could substantially elevate circulating serotonin concentrations, potentially explaining the digital vasoconstriction and ischaemic pathology observed in acute laminitis. For practitioners, this work underscores how disruption of normal caecal fermentation and bacterial translocation during nutritional or metabolic challenges might trigger vasoconstrictor-mediated laminitis through serotonergic mechanisms.
Read the full abstract on PubMed
Practical Takeaways
- •Carbohydrate overload that triggers endotoxin release and dietary amines may elevate plasma 5-HT and contribute to laminitis pathogenesis through digital vasoconstriction
- •Managing hindgut fermentation and limiting dietary triggers is important in laminitis prevention since 5-HT-mediated vasoconstriction affects digital blood flow
- •This mechanistic research supports careful nutritional management during acute laminitis cases, as reducing endotoxin and dietary amine sources may help preserve digital perfusion
Key Findings
- •Equine platelet 5-HT uptake has a Km of 2.4 ± 0.6 micromol/l and Vmax of 8.3 ± 0.6 pmol/10⁷ platelets/min, representing a saturable process
- •Four naturally occurring monoamines inhibited 5-HT uptake noncompetitively, decreasing Vmax by 17-82%
- •Endotoxin (LPS) with leucocytes released 3.8 ± 1.7 pmol 5-HT/10⁷ platelets via platelet activating factor (PAF) mechanism
- •Increased plasma 5-HT concentrations from impaired uptake and endotoxin-induced release may cause selective vasoconstriction in equine digital circulation