Characterization of putative 5‐ht7 receptors mediating direct relaxation in Cynomolgus monkey isolated jugular vein

1 5‐Hydroxytryptamine (5‐HT) receptors mediating contraction and relaxation are present in Cynomolgus monkey isolated jugular vein denuded of endothelium. 2 In the absence of spasmogen, α‐methyl‐5‐HT and sumatriptan contracted the tissues with potency values (pEC 50 ) of 6.8 ( n =2) and 6.4 ± 0.1 (mean ± s.e. mean, n =3), respectively. In contrast, 5‐HT caused an initial contraction (10 nM‐1 μ m ), followed by relaxation (1 μ m ‐32 μ m ). The contractile effect of α‐methyl‐5‐HT was antagonized by ketanserin with a pK B value of 8.1 ( n =2). 5‐Carboxamidotryptamine (5‐CT), 5‐methoxytryptamine (5‐MeOT) and 8‐OH‐DPAT did not contract or relax the tissues in the absence of spasmogen. 3 In tissues precontracted with U46619 (10 nM) and in the presence of 5‐HT 1A , 5‐HT 1B , 5‐HT 2A , 5‐HT 3 , and 5‐HT 4 receptor blockade, 5‐CT and 5‐MeOT caused endothelium‐independent relaxation with potency values of 7.5±0.1 ( n =21) and 5.7±0.1 ( n =4), respectively. The potency of 5‐HT was 7.2 ( n =2) while α‐methyl‐5‐HT did not start to relax the tissues below a concentration of 10 μ m . 4 Relaxations elicited by 5‐CT were antagonized by the following compounds (with pK B values in parentheses): methiothepin (9.7), mesulergine (8.1), metergoline (8.0), clozapine (7.8), mianserin (7.7), spiperone (7.3), ritanserin (7.1), methysergide (7.0) and ketanserin (5.7). 5 It is concluded that the 5‐HT receptor mediating endothelium‐independent relaxation may be a functional correlate of the putative 5‐ht 7 receptor.