5‐HT 7 receptors mediate the inhibitory effect of 5‐HT on peristalsis in the isolated guinea‐pig ileum

The study was undertaken to investigate the 5‐HT receptor mediating the inhibitory effect of 5‐HT on peristalsis in the guinea‐pig isolated ileum. The facilitatory and inhibitory effects were measured as the decrease and increase, respectively, in the intraluminal pressure required to trigger peristalsis. In the presence of 5‐HT 2/3&4 receptor antagonists ketanserin (0.1 μ M ), granisetron (1 μ M ) and SB‐204070 (1 μ M ), a cumulative addition (0.1–100 μ M ) of 5‐HT or 5‐carboxamidotryptamine, but not 2‐methyl‐5‐HT produced a concentration‐dependent increase in the threshold required to trigger peristalsis. The 5‐HT 7 receptor selective antagonist SB‐269970‐A (0.01–1 μ M ) or methiothepin (0.01–0.1 μ M ) concentration‐dependently antagonised this response to 5‐HT. SB‐269970‐A (1 μ M ) and methiothepin (1 μ M ) were also able to restore peristalsis in tissues in which peristalsis was inhibited by a prior addition of 30 μ M of 5‐HT. The results indicate an involvement of 5‐HT 7 receptors in the inhibitory effect of 5‐HT on peristalsis in the guinea‐pig ileum. British Journal of Pharmacology (2003) 138 , 1210–1214. doi: 10.1038/sj.bjp.0705184