Contractile effects of 5-hydroxytryptamine (5-HT) in the equine jejunum circular muscle: functional and immunohistochemical identification of a 5-HT1A-like receptor.
Authors: Delesalle C, van Acker N, Claes P, Deprez P, de Smet I, Dewulf J, Lefebvre R A
Journal: Equine veterinary journal
Summary
# Serotonin receptors in equine small intestine: implications for prokinetic therapy Prokinetic drugs commonly used in human medicine to treat gastrointestinal ileus have shown inconsistent efficacy in horses, partly because the serotonin receptor subtypes involved in equine intestinal motility remain poorly characterised. Delesalle and colleagues used isometric organ-bath recordings on isolated equine jejunal circular muscle tissue combined with immunohistochemistry to identify which serotonin receptors mediate contractile responses. Their receptor antagonist studies systematically excluded involvement of 5-HT1B, 1D, 2A, 3, 4 and 7 receptor subtypes, whilst selective 5-HT1A antagonists (WAY 100635 and NAN 190) produced clear rightward shifts in the serotonin dose-response curve, identifying a 5-HT1A-like receptor as the functionally active subtype; immunofluorescence subsequently confirmed the presence of these receptors in the muscularis mucosae and both circular and longitudinal smooth muscle layers. Critically, this research reveals that equine intestinal smooth muscle contracts via 5-HT1A receptors rather than the 5-HT4 receptors targeted by most conventional prokinetics, which may explain their limited effectiveness in horses and suggests that alternative pharmacological strategies—potentially involving 5-HT1A agonists—warrant investigation. The anatomical distribution of these receptors across multiple muscular layers indicates substantial therapeutic potential if appropriate agonists can be developed to enhance jejunal contractility without neuronal or nitric oxide-mediated confounding effects.
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Practical Takeaways
- •Current prokinetic drugs targeting 5-HT4 receptors may be ineffective in horses because equine jejunum primarily uses 5-HT1A-like receptors for contractile responses; future prokinetic development should target 5-HT1A receptors instead
- •Understanding species-specific serotonin receptor physiology explains why gastrointestinal prokinetics effective in humans show equivocal results in equine ileus cases
- •5-HT1A receptor agonists may represent a novel therapeutic approach for treating equine gastrointestinal motility disorders
Key Findings
- •5-HT induces tonic contractions in equine jejunal circular muscle through 5-HT1A-like receptors, independent of neural or nitric oxide pathways
- •5-HT1A receptor antagonists WAY 100635 and NAN 190 caused rightward shift of 5-HT concentration-response curve, confirming 5-HT1A-like receptor involvement
- •Immunohistochemistry confirmed presence of 5-HT1A receptors in muscularis mucosae and both longitudinal and circular smooth muscle layers of equine jejunum
- •5-HT1A-like receptors, not 5-HT4 receptors, mediate contractile responses in equine small intestine, contrasting with human prokinetic drug targets