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.

This study examines the presence and role of 5-hydroxytryptamine 4 (5-HT4) receptors in the intestinal smooth muscle of horses without gastrointestinal disease. Their effect on contractility and the potential therapeutic use of the drug tegaserod was also investigated.

Methodology

• The researchers used smooth muscle samples from the duodenum, ileum, and pelvic flexure of 24 horses without any signs of gastrointestinal disease. These samples were collected immediately post-mortem.
• The contractile responses of the smooth muscle preparations to 5-hydroxytryptamine and electric field stimulation were measured inside an isometric organ bath. The effect of tegaserod, both alone and in combination with 5-hydroxytryptamine, on the contractility of the intestinal tissues was also investigated.
• An immunofluorescence technique was utilized to identify the presence and distribution of 5-HT4 receptors in the intestinal tissues and to determine whether they were located on interstitial cells of Cajal (specialized cells that control smooth muscle contraction).

Findings

• 5-HT4 receptor immunoreactivity was observed across all smooth muscle layers of the intestinal tissues. However, the receptors were not found on the myenteric plexus or the interstitial cells of Cajal.
• The drug tegaserod had a noticeable effect on the tissues. In samples from the duodenum and pelvic flexure stimulated by an electrical field, tegaserod increased the amplitude of smooth muscle contractions in a dose-dependent manner.
• When preincubated with tegaserod, the baseline tone of the 5-HT-induced contractility in small intestine samples decreased when compared to the effect of 5-HT alone, confirming that tegaserod acts as a partial agonist.

Conclusions

• The study concluded that 5-HT4 receptors play a significant role in the contractile response of the horse’s intestinal tract to 5-hydroxytryptamine.
• Based on the observed effects of tegaserod, the researchers suggested that this drug could potentially be useful in treating horses with reduced gastrointestinal motility.