Evidence for 5‐HT 7 receptors mediating relaxation of human colonic circular smooth muscle

5‐HT 4 receptors mediate relaxation of human colon circular muscle. However, after 5‐HT 4 receptor blockade (SB 204070 10 n M ), 5‐HT still induced a relaxation (pEC 50 6.3). 5‐HT 4 receptors were sufficiently blocked, as the curves to 5‐HT obtained in the presence of 10 and 100 n M SB 204070 were indistinguishable. This 5‐HT‐induced relaxation was tetrodotoxin‐insensitive, indicative of a smooth muscle relaxant 5‐HT receptor. This, and the rank order of potency (5‐CT=5‐MeOT=5‐HT) suggested involvement of 5‐HT 1 or 5‐HT 7 receptors. Mesulergine, a 5‐HT 7 receptor antagonist at nanomolar concentrations, and a 5‐HT 1 receptor antagonist at micromolar concentrations, competitively antagonized the 5‐HT‐induced relaxation (pK B 8.3) and antagonized the relaxation to 5‐CT. Methysergide antagonized the 5‐HT‐induced relaxation (pA 2 7.6). It is concluded that the profile of the smooth muscle inhibitory 5‐HT receptor resembles that of the 5‐HT 7 receptor. These data provide the first evidence for functional human 5‐HT 7 receptors. British Journal of Pharmacology (1999) 128 , 849–852; doi: 10.1038/sj.bjp.0702762