Contractile effects of 5‐hydroxytryptamine (5‐HT) in the equine jejunum circular muscle: Functional and immunohistochemical identification of a 5‐HT 1A ‐like receptor

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Abstract
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‐hydroxytryptamine 4 (5‐HT 4 ) 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 N G ‐nitro‐L‐arginine did not modify this response. A set of 5‐HT receptor subtype selective antagonists excluded interaction with 5‐HT 1B, 1D, 2A, 3, 4 and 7 receptors. The selective 5‐HT 1A 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‐HT 1A, 1B, 1D, 5 and 7 receptors was also antagonised by WAY 100635, identifying the targeted 5‐HT receptor as a 5‐HT 1A ‐like receptor. Immunohistology performed with rabbit polyclonal anti‐5‐HT 1A receptor antibodies confirmed the presence of muscular 5‐HT 1A 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‐HT 1A ‐like receptors. Potential relevance : The lack of evidence for presence of 5‐HT 4 receptors in the equine small intestine questions the use of human prokinetic drugs acting at 5‐HT 4 receptors in horses with small intestinal ileus.

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