The 5-HT4 receptor agonist prucalopride does not facilitate cholinergic neurotransmission in circular and longitudinal smooth muscle preparations of equine mid-jejunum.

The research examines the effect of a drug, prucalopride, on the smooth muscle of horse intestines. Researchers found that prucalopride, which is a selective 5-HT receptor agonist, does not facilitate cholinergic neurotransmission, implying that this receptor type may not occur in the horse intestines.

Research Objective

The main objective of this study was to identify whether the 5-HT receptors, also known as serotonin receptors, were functional in the mid-section of the horse’s intestines (jejunum). This was explored using an experimental model and assessing the effects of the drug prucalopride, known to act on these receptors.

Methods

• The researchers conducted an in vitro study, which means the experiments were performed outside of a living organism, in this case, on muscle strips from the horse’s jejunum.
• These muscle strips were mounted in special baths and exposed to electrical field stimulation (EFS) to stimulate contractions and measure the muscle’s response.
• To investigate how prucalopride might affect the muscle contractions, the researchers applied the drug and then induced submaximal cholinergic contractions at a single voltage. This allowed them to measure and compare the muscle response with and without the drug present.

Results

• The study found that the electrical stimulation induced contractions in the muscle strips, and that these contractions were primarily driven by cholinergic mechanism, as they could be blocked by atropine, a known anti-cholinergic substance.
• When prucalopride was introduced, there was no evident change or enhancement to these contractions, suggesting that the 5-HT receptors, on which the drug was expected to act, were not functional in these muscles. Also, prucalopride did not influence muscle tone that was continuously enhanced with potassium chloride (KCl).
• The research team also tested with the full 5-HT receptor agonist 5-HT and observed similar results – there was no noticeable effect on the induced cholinergic contractions.

Conclusion

The researchers concluded that there appear to be no functional 5-HT receptors on the cholinergic neurons nor muscular 5-HT receptors in the horse’s jejunum. This suggests that prucalopride and similar serotonin receptor agonists may not be effective in manipulating gut motility in horses. It also opens up new questions about the types and locations of receptors in horses and similar species.