5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist.
The effects of 5-hydroxytryptamine (5-HT), HTF 919, a new 5-HT(4) agonist, and the antagonists SB 203-186 (5-HT(4)) and tropisetron (5-HT(3)) on intestinal motility were tested in vitro on isolated preparations of horse ileum and pelvic flexure. Concentration-response curves were created by cumulative application of the agonists with or without preincubation of the antagonists. The 5-HT preparation induced a concentration-dependent contraction in equine ileum and pelvic flexure. The results indicate that 5-HT receptors are present in all parts of equine intestine investigated in this study. Tropisetron was found to act as a noncompetitive antagonist in all locations of the equine intestine. SB 203-106 was confirmed as an antagonist to 5-HT in the equine ileum circular muscle, in pelvic flexure circular and longitudinal muscle. Nevertheless, a discernible increase of smooth muscle contractions caused by HTF 919 could only be observed in pelvic flexure. In accordance with an earlier study in the guinea pig, in the equine gut HTF 919 acted as a partial agonist for the 5-HT(4) receptor with an affinity constant in the nanomolar range. It is concluded that 5-HT receptors, and especially their subtypes, may represent a promising target for the treatment and prevention of gastrointestinal (GI) motility disorders in horses.
Weiss
R
R
Institute of Veterinary Pharmacology, University of Bern, CH-3012 Bern, Switzerland.
Abel
D
D
Scholtysik
G
G
Straub
R
R
Mevissen
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005769:Gastrointestinal Motility; D006736:Horses / Q000502:physiology*; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D017773:Pelvic Floor / Q000502:physiology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000077526:Tropisetron
C088817:(1-piperidinyl)ethyl 1H-indole-3-carboxylate; D007211:Indoles; D010880:Piperidines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000077526:Tropisetron