Contractile effects of 5-hydroxytryptamine (5-HT) in the equine jejunum circular muscle: functional and immunohistochemical identification of a 5-HT1A-like receptor.
BACKGROUND
Prokinetic drugs used to treat gastrointestinal ileus in man have equivocal results in horses. In man, prokinetic drugs have 5-hydroxytryptamine4(5-HT4) receptors as their target, but little is known about the 5-HT-receptor subtypes in the equine small intestine.


OBJECTIVE
Functional and immunohistochemical identification of the serotonin receptor subtype(s) responsible for the 5-HT induced contractile response in the equine circular jejunum.


METHODS
Isometric organ-bath recordings were carried out to assess spontaneous and drug-evoked contractile activity of equine circular jejunum. Histological investigations by immunofluorescence analyses were performed to check for presence and localisation of this functionally identified 5-HT receptor subtype.


RESULTS
Tonic contractions were induced by 5-HT in horse jejunal circular muscle. Tetrodotoxin, atropine and NG-nitro L-arginine did not modify this response. A set of 5-HT receptor subtype selective antagonists excluded interaction with 5-HT1B, 1D, 2A, 3, 4 and 7 receptors. The selective 5-HT1A receptor antagonists WAY 100635 and NAN 190 caused a clear rightward shift of the concentration-response curve to 5-HT. The contractile effect of 5-CT, that can interact with 5-HT1A, 1B, 1D, 5 and 7 receptors was also antagonised by WAY 100635, identifying the targeted 5-HT receptor as a 5-HT1A-like receptor. Immunohistology performed with rabbit polyclonal anti-5-HT1A receptor antibodies confirmed the presence of muscular 5-HT1A receptors in the muscularis mucosae, and both longitudinal and circular smooth muscle layers of the equine jejunum.


CONCLUSIONS
Contractile responses in equine jejunal circular smooth muscle induced by 5-HT involves 5-HT1A-like receptors.
Delesalle
C
C
Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium.
van Acker
N
N
Claes
P
P
Deprez
P
P
de Smet
I
I
Dewulf
J
J
Lefebvre
R A
RA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy* / Q000473:pathology; D006736:Horses; D045823:Ileus / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D007150:Immunohistochemistry / Q000662:veterinary; D007583:Jejunum; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D044282:Receptor, Serotonin, 5-HT1A / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology*
D018490:Serotonin Agents; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin