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.
OBJECTIVE
To evaluate the expression of the 5-hydroxytryptamine 4 (5-HT4) receptor subtype and investigate the modulating function of those receptors on contractility in intestinal tissues obtained from horses without gastrointestinal tract disease.


METHODS
Smooth muscle preparations from the duodenum, ileum, and pelvic flexure collected immediately after slaughter of 24 horses with no history or signs of gastrointestinal tract disease.


METHODS
In isometric organ baths, the contractile activities of smooth muscle preparations in response to 5-hydroxytryptamine and electric field stimulation were assessed; the effect of tegaserod alone or in combination with 5-hydroxytryptamine on contractility of intestinal specimens was also investigated. Presence and distribution of 5-HT4 receptors in intestinal tissues and localization on interstitial cells of Cajal were examined by use of an immunofluorescence technique.


RESULTS
Widespread 5-HT4 receptor immunoreactivity was observed in all intestinal smooth muscle layers; 5-HT4 receptors were absent from the myenteric plexus and interstitial cells of Cajal. In electrical field-stimulated tissue preparations of duodenum and pelvic flexure, tegaserod increased the amplitude of smooth muscle contractions in a concentration-dependent manner. Preincubation with tegaserod significantly decreased the basal tone of the 5-HT-evoked contractility in small intestine specimens, compared with the effect of 5-HT alone, thereby confirming that tegaserod was acting as a partial agonist.


CONCLUSIONS
In horses, 5-HT4 receptors on smooth muscle cells appear to be involved in the contractile response of the intestinal tract to 5-hydroxytryptamine. Results suggest that tegaserod may be useful for treatment of reduced gastrointestinal tract motility in horses.
Division of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Berne, 3012 Berne, Switzerland.
Andrea S
AS
Prause
Christophe T
CT
Guionaud
Michael H
MH
Stoffel
Christopher J
CJ
Portier
Meike
M
Mevissen
D000003:Abattoirs; D000818:Animals; D004386:Duodenum / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D005455:Fluorescent Antibody Technique; D005767:Gastrointestinal Diseases / Q000662:veterinary; D006736:Horses; D007082:Ileum / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D010388:Pelvis / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D007211:Indoles; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C105050:tegaserod; D019009:Proto-Oncogene Proteins c-kit