Contractile effects of 5‐hydroxytryptamine and 5‐carboxamidotryptamine in the equine jejunum

The use of human prokinetic drugs in colic horses leads to inconsistent results. This might be related to differences in gastrointestinal receptor populations. The motor effects of 5‐hydroxytryptamine (5‐HT; serotonin) on the equine mid‐jejunum were therefore studied. Longitudinal muscle preparations were set up for isotonic measurement. 5‐HT induced tonic contractions with superimposed phasic activity; these responses were not influenced by tetrodotoxin and atropine, suggesting a non‐neurogenic, non‐cholinergic pathway. The 5‐HT receptor antagonists GR 127935 (5‐HT 1B,D ), ketanserin (5‐HT 2A ), SB 204741 (5‐HT 2B ), RS 102221 (5‐HT 2C ), granisetron (5‐HT 3 ), GR 113808 (5‐HT 4 ) and SB 269970 (5‐HT 7 ) had no influence on the 5‐HT‐induced response; the 5‐HT 1A receptor antagonists NAN 190 (p K b =8.13±0.06) and WAY 100635 (p K b =8.69±0.07), and the 5‐HT 1,2,5,6,7 receptor antagonist methysergide concentration‐dependently inhibited the 5‐HT‐induced contractile response. The 5‐HT 1,7 receptor agonist 5‐carboxamidotryptamine (5‐CT) induced a contractile response similar to that of 5‐HT; its effect was not influenced by tetrodotoxin and atropine, and SB 269970, but antagonised by WAY 100635. 8‐OHDPAT, buspiron and flesinoxan, which are active at rat and human 5‐HT 1A receptors, had no contractile influence. These results suggest that the contractile effect of 5‐HT in equine jejunal longitudinal muscle is due to interaction with muscular 5‐HT receptors, which cannot be characterised between the actually known classes of 5‐HT receptors.British Journal of Pharmacology (2006) 147 , 23–35. doi: 10.1038/sj.bjp.0706431