In vitro effects of 5-hydroxytryptamine and cisapride on the circular smooth muscle of the jejunum of horses.

The study identifies how cisapride and 5-hydroxytryptamine (5-HT) affect the circular smooth muscle of the jejunum in horses, which can impact treatments for postoperative ileus, a common condition of gastrointestinal obstruction in horses.

Methodology

• The researchers used jejunal muscle strips from eight horses for the experiment.
• The muscle strips were suspended in isolated muscle baths to record the experiments.
• They then measured the isometric stress responses to 5-HT and cisapride, with and without specific antagonists, to observe the reactions.
• These reactions would reveal how the muscle tension changes when introduced to 5-HT and cisapride and if the presence of specific antagonists changes the responses.

Results

• In the presence of atropine and tetrodotoxin, the muscle strips responded to 5-HT and cisapride with an increase in contractile force: a measure of the muscle’s strength and activity.
• Increased concentrations of 5-HT produced an increase in contractile amplitude and the maximum response was measured at 1,151+/-214 g/cm2 with a molar concentration of 0.028+/-0.002 microM which induces contractile force equal to half of the maximum response. This indicates that the muscle response is directly proportional to the concentration of 5-HT introduced.
• Using the 5-HT2 antagonist ketanserin before incubation reduced the maximum response of 5-HT by almost half (626 +/-147 g/cm2) and the potency of 5-HT increased substantially (0.307+/-0.105 microM).
• The use of the 5-HT3 antagonist tropisetron before incubation also reduced the efficacy of 5-HT to nearly three-quarters (894+/-184 g/cm2).
• Cisapride also illustrated a concentration-dependent increase in contractile amplitude, which was considerably lesser than 5-HT, with a maximum response of 331+/-82 g/cm2 and an EC50 of 0.302+/-0.122 microM.
• Ketanserin before incubation drastically reduced the maximum response of cisapride to a fifteenth of its original (55+/-17 g/cm2) and increased the potency of cisapride slightly (0.520+/-0.274 microM).

Conclusions

• According to the results, the stimulatory effects of 5-HT and cisapride on circular smooth muscle of the horse’s jejunum are primarily through a noncholinergic effect. That means the observed activity not involved in the neurotransmitter acetylcholine.
• The effects of 5-HT are mediated at least partially, by 5-HT2 and 5-HT3 receptors, meaning these specific receptors respond to the introduction of 5-HT and signal a response.
• The effects of cisapride are primarily mediated by 5-HT2 receptors, indicating that cisapride mainly interacts with this type of receptor in the muscle tissues.
• These findings can be beneficial for improving treatment strategies for horses with postoperative ileus by understanding how drugs like cisapride can help stimulate gastrointestinal activity.