Contractile effects of 5-hydroxytryptamine (5-HT) in the equine jejunum circular muscle: Functional and immunohistochemical identification of a 5-HT1A-like receptor

Summary Reasons for performing study: Prokinetic drugs used to treat gastrointestinal ileus in man have equivocal results in horses. In man, prokinetic drugs have 5-hydroxytryptamine4 (5-HT4) receptors as their target, but little is known about the 5-HT-receptor subtypes in the equine small intestine. Objective: Functional and immunohistochemical identification of the serotonin receptor subtype(s) responsible for the 5-HT induced contractile response in the equine circular jejunum. Methods: Isometric organ-bath recordings were carried out to assess spontaneous and drug-evoked contractile activity of equine circular jejunum. Histological investigations by immunofluorescence analyses were performed to check for presence and localisation of this functionally identified 5-HT receptor subtype. Results: Tonic contractions were induced by 5-HT in horse jejunal circular muscle. Tetrodotoxin, atropine and NG-nitro-L-arginine did not modify this response. A set of 5-HT receptor subtype selective antagonists excluded interaction with 5-HT1B, 1D, 2A, 3, 4 and 7 receptors. The selective 5-HT1A receptor antagonists WAY 100635 and NAN 190 caused a clear rightward shift of the concentration-response curve to 5-HT. The contractile effect of 5-CT, that can interact with 5-HT1A, 1B, 1D, 5 and 7 receptors was also antagonised by WAY 100635, identifying the targeted 5-HT receptor as a 5-HT1A-like receptor. Immunohistology performed with rabbit polyclonal anti-5-HT1A receptor antibodies confirmed the presence of muscular 5-HT1A receptors in the muscularis mucosae, and both longitudinal and circular smooth muscle layers of the equine jejunum. Conclusions: Contractile responses in equine jejunal circular smooth muscle induced by 5-HT involves 5-HT1A-like receptors. Potential relevance: The lack of evidence for presence of 5-HT4 receptors in the equine small intestine questions the use of human prokinetic drugs acting at 5-HT4 receptors in horses with small intestinal ileus.