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

Jorge E. NietoComparative Gastroenterology Laboratory, Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, CA 95616.

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Jack R. SnyderComparative Gastroenterology Laboratory, Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, CA 95616.

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Cynthia Kollias-BakerKL Maddy Equine Analytical Chemistry Laboratory, University of California, Davis, CA 95616.

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Scott StanleyKL Maddy Equine Analytical Chemistry Laboratory, University of California, Davis, CA 95616.

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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 (Emax) 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 Emax (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 (Emax, 894 ± 184 g/cm2) to 5-HT. Cisapride also caused a concentrationdependent increase in contractile amplitude, with an Emax of 331 ± 82 g/cm2 and an EC50 of 0.302 ± 0.122 µM. Prior incubation with ketanserin decreased the Emax (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. (Am J Vet Res 2000;61:1561–1565)

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 (Emax) 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 Emax (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 (Emax, 894 ± 184 g/cm2) to 5-HT. Cisapride also caused a concentrationdependent increase in contractile amplitude, with an Emax of 331 ± 82 g/cm2 and an EC50 of 0.302 ± 0.122 µM. Prior incubation with ketanserin decreased the Emax (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. (Am J Vet Res 2000;61:1561–1565)