Characterization of the receptors involved in the 5‐HT‐induced excitation of canine antral longitudinal muscle

We aimed to characterize the 5‐HT receptors involved in the 5‐HT‐induced effect on electrically induced contractions of dog antrum longitudinal muscle in vitro . In the presence of L ‐NOARG (0.1 m M ), electrical field stimulation (EFS) induced atropine‐ and tetrodotoxin‐sensitive contractions. Tetrodotoxin or atropine left any agonist tested ineffective. These EFS‐induced contractions were on average enhanced by 5‐HT (0.3 μ M ), however, pronounced variation in the response to 5‐HT was observed. There were non‐significant trends of the selective 5‐HT 3 receptor antagonist granisetron (1 μ M ), and methysergide (1 μ M ; preventing interactions of 5‐HT with 5‐HT 1 , 5‐HT 2 , 5‐ht 5 , 5‐HT 6 and 5‐HT 7 receptors) to increase the response to 5‐HT. The selective 5‐HT 4 receptor antagonist GR 113808 (0.1 μ M ) displayed a non‐significant trend to inhibit the 5‐HT‐induced increase. Combination experiments with methysergide (1 μ M ), granisetron (1 μ M ) and GR 113808 (0.1 μ M ) revealed that the 5‐HT (0.3 μ M )‐induced response consisted of (1) an excitatory component blocked by GR 113808, (2) excitatory and inhibitory components both blocked by methysergide. The selective 5‐HT 4 receptor agonist prucalopride (0.3 μ M ) increased EFS‐induced contractions, an effect prevented by GR 113808 (0.1 μ M ). The increase of EFS‐induced contractions by the preferential 5‐HT 2 receptor agonist α‐Me‐5‐HT (0.3 μ M ) was antagonized by 5‐HT 2B receptor antagonists. The 5‐HT 1 /5‐HT 7 receptor agonist 5‐carboxamidotryptamine (5‐CT; 0.3 μ M ) inhibited EFS‐induced contractions. This was prevented by methysergide (1 μ M ), the 5‐HT 7 receptor antagonist mesulergine (0.3 μ M ) and the selective 5‐HT 7 receptor antagonist SB‐269970 (0.3 μ M ). In the presence of GR 113808 (0.1 μ M ), α‐Me‐5‐HT (1 μ M ) increased EFS‐induced contractions. The 5‐HT (0.3 μ M )‐induced inhibition of the stimulation by α‐Me‐5‐HT was prevented by SB‐269970 (0.3 μ M ). In conclusion, dog antral longitudinal muscle is endowed with (1) excitatory neuronal 5‐HT 4 receptors and 5‐HT 2B receptors and (2) inhibitory smooth muscle 5‐HT 7 receptors.British Journal of Pharmacology (2001) 134 , 1351–1359; doi: 10.1038/sj.bjp.0704376