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

Abstract

1. 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. 2. In the presence of L-NOARG (0.1 mM), 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 μM), however, pronounced variation in the response to 5-HT was observed. There were non-significant trends of the selective 5-HT3 receptor antagonist granisetron (1 μM), and methysergide (1 μM; preventing interactions of 5-HT with 5-HT1, 5-HT2, 5-HT5, 5-HT6 and 5-HT7 receptors) to increase the response to 5-HT. The selective 5-HT4 receptor antagonist GR 113808 (0.1 μM) displayed a non-significant trend to inhibit the 5-HT-induced increase. 3. Combination experiments with methysergide (1 μM), granisetron (1 μM) and GR 113808 (0.1 μM) revealed that the 5-HT (0.3 μM)-induced response consisted of (1) an excitatory component blocked by GR 113808, (2) excitatory and inhibitory components both blocked by methysergide. 4. The selective 5-HT4 receptor agonist prucalopride (0.3 μM) increased EFS-induced contractions, an effect prevented by GR 113808 (0.1 μM). 5 The increase of EFS-induced contractions by the preferential 5-HT2 receptor agonist α-Me-5-HT (0.3 μM) was antagonized by 5-HT2B receptor antagonists. 6. The 5-HT1/5-HT7 receptor agonist 5-carboxamidotryptamine (5-CT; 0.3 μM) inhibited EFS-induced contractions. This was prevented by methysergide (1 μM), the 5-HT7 receptor antagonist mesulergine (0.3 μM) and the selective 5-HT7 receptor antagonist SB-269970 (0.3 μM). 7. In the presence of GR 113808 (0.1 μM), α-Me-5-HT (1 μM) increased EFS-induced contractions. The 5-HT (0.3 μM)-induced inhibition of the stimulation by α-Me-5-HT was prevented by SB-269970 (0.3 μM). 8. In conclusion, dog antral longitudinal muscle is endowed with (1) excitatory neuronal 5-HT4 receptors and 5-HT2B receptors and (2) inhibitory smooth muscle 5-HT7 receptors.