Characterization of a postjunctional 5-HT receptor mediating relaxation of guinea-pig isolated ileum

The 5-HT receptor mediating postjunctional relaxation of precontracted guinea-pig ileum has been characterized using several agonists and antagonists. Substance P precontracted tissues were potently relaxed by 5-HT (5-hydroxytryptamine, serotonin), 5-CT (5-carboxamidotryptamine) and several other indoles. The rank order of potency, with pEC50 values in parentheses, was 5-CT (7.6)5-methoxytryptamine (5.7)5-HT (5.5)alpha-methyl-5-HT (4.7)2-methyl-5-HT (4.0) = tryptamine (4.0) = N,N-dimethyl-tryptamine (4.0) = N,N-dimethyl-5-HT (4.0) = dipropyl-5-CT (4.0) = sumatriptan (4.0). 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) acted as a potent (6.3), but partial, agonist with respect to 5-HT. The responses to 5-CT were antagonized by several compounds with the following rank order of affinity, with pKB values in parentheses: LSD (lysergic acid diethylamide; 8.1) = mesulergine (7.8)methysergide (7.6) = spiperone (7.6)clozapine (7.3)(-)-pindolol (6.0)ketanserin (6.0) = ondansetron (6.0) = GR 113808 ([1-(2-methane-sulphonamido-ethyl)-piperidin-4-yl]-methyl-in dole-3- carboxylate maleate;6.0). The relaxant responses to 5-HT were also resistant to tetrodotoxin. These data are consistent with a functional 5-HT receptor, mediating relaxation of guinea-pig ileum, which exhibits an operational profile similar to that of the cloned guinea-pig 5-ht7 receptor. This study, therefore, provides evidence for a functional correlate of the 5-ht7 gene product.