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

Abstract

Objective - To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses. Sample Population - Jejunal muscle strips from 8 horses. Procedure - Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined. Results - Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (E(max)) of 1, 151 ± 214 g/cm2 and a molar concentration that induces contractile force equal to 50% of maximum response (EC50) of 0.028 ± 0.002 μM. Prior incubation with the 5-HT2 antagonist ketanserin decreased the E(max) (626 ± 147 g/cm2) and potency (EC50, 0.307 ± 0.105 μM) of 5-HT. Prior incubation with the 5-HT3 antagonist tropisetron decreased the efficacy (E(max), 894 ± 184 g/cm2) to 5-HT. Cisapride also caused a concentration-dependent increase in contractile amplitude, with an E(max) of 331 ± 82 g/cm2 and an EC50 of 0.302 ± 0.122 μM. Prior incubation with ketanserin decreased the E(max) (55 ± 17 g/cm2) and potency (EC50, 0.520 ± 0.274 μM) of cisapride. Conclusion and Clinical Relevance - Stimulatory effects of 5-HT and cisapride on circular smooth muscle of equine jejunum are mediated primarily through a noncholinergic effect. The effects of 5-HT are mediated, at least partially, by 5-HT2 and 5-HT3 receptors, whereas the effects of cisapride are mediated primarily by 5-HT2 receptors. This may impact treatment of horses with postoperative ileus.