Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure.
In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT(7) receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively. 5-HT(7) immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT(7) immunoreactivity. The selective 5-HT(7) receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently. Our in vitro experiments suggest an involvement of the 5-HT(7) receptor subtype in contractility of equine intestine. While the 5-HT(7) receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT(7) receptor ligand SB-269970, suggesting it exerting inverse agonist properties.
Division Veterinary Pharmacology and Toxicology, University of Berne, 3012 Berne, Switzerland.
Andrea S
AS
Prause
Michael H
MH
Stoffel
Christopher J
CJ
Portier
Meike
M
Mevissen
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004386:Duodenum / Q000502:physiology*; D005767:Gastrointestinal Diseases / Q000453:epidemiology / Q000662:veterinary*; D006734:Horse Diseases / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D006736:Horses; D007082:Ileum / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D017773:Pelvic Floor / Q000502:physiology; D010636:Phenols / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D012307:Risk Factors; D013449:Sulfonamides / Q000494:pharmacology
D015415:Biomarkers; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D013449:Sulfonamides; C104425:serotonin 7 receptor