Expression and function of 5-hydroxytryptamine 4 receptors in smooth muscle preparations from the duodenum, ileum, and pelvic flexure of horses without gastrointestinal tract disease

摘要

Objective-To evaluate the expression of the 5-hydroxytryptamine 4 (5-HT4) receptor subtype and investigate the modulating function of those receptors on contractility in intestinal tissues obtained from horses without gastrointestinal tract diseaseSample Population-Smooth muscle preparations from the duodenum ileum and pelvic flexure collected immediately after slaughter of 24 horses with no history or signs of gastrointestinal tract diseaseProcedures-In isometric organ baths the contractile activities of smooth muscle preparations in response to 5-hydroxytryptamine and electric field stimulation were assessed the effect of tegaserod alone or in combination with 5-hydroxytryptamine on contractility of intestinal specimens was also investigated Presence and distribution of 5-HT4 receptors in intestinal tissues and localization on interstitial cells of Cajal were examined by use of an immunofluorescence techniqueResults-Widespread 5-HT4 receptor immunoreactivity was observed in all intestinal smooth muscle layers 5 HT4 receptors were absent from the myenteric plexus and interstitial cells of Cajal In electrical field stimulated tissue preparations of duodenum and pelvic flexure tegaserod increased the amplitude of smooth muscle contractions in a concentration dependent manner Preincubation with tegaserod significantly decreased the basal tone of the 5-HT evoked contractility in small intestine specimens compared with the effect of 5-HT alone thereby confirming that tegaserod was acting as a partial agonistConclusions and Clinical Relevance-In horses 5 HT4 receptors on smooth muscle cells appear to be involved in the contractile response of the intestinal tract to 5-hydroxytryptamine Results suggest that tegaserod may be useful for treatment of reduced gastrointestinal tract motility in horses (Am J Vet Res 2010 71 1432-1442)