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, alpha-methyl-5-HT and sumatriptan contracted the tissues with potency values (pEC50) 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 microM), followed by relaxation (1 microM - 32 microM). The contractile effect of alpha-methyl-5-HT was antagonized by ketanserin with a pKB 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-HT1A, 5-HT1B, 5-HT2A, 5-HT3, and 5-HT4 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 alpha-methyl-5-HT did not start to relax the tissues below a concentration of 10 microM. 4. Relaxations elicited by 5-CT were antagonized by the following compounds (with pKB 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-ht7 receptor.
Leung
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Institute of Pharmacology, Roche Bioscience, Palo Alto, CA 94304, USA.
Walsh
L K
LK
Pulido-Rios
M T
MT
Eglen
R M
RM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects* / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
D011450:Prostaglandin Endoperoxides, Synthetic; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C047087:5-carboxamidotryptamine