5-HT7 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-HT2/3&4 receptor antagonists ketanserin (0.1 mum), granisetron (1 mum) and SB-204070 (1 mum), a cumulative addition (0.1 - 100 mum) 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-HT7 receptor selective antagonist SB-269970-A (0.01-1 mum) or methiothepin (0.01-0.1 mum) concentration-dependently antagonised this response to 5-HT. SB-269970-A (1 mum) and methiothepin (1 mum) were also able to restore peristalsis in tissues in which peristalsis was inhibited by a prior addition of 30 mum of 5-HT. The results indicate an involvement of 5-HT7 receptors in the inhibitory effect of 5-HT on peristalsis in the guinea-pig ileum.