CHARACTERIZATION OF PUTATIVE 5-HT(7) RECEPTORS MEDIATING DIRECT RELAXATION IN CYNOMOLGUS MONKEY ISOLATED JUGULAR-VEIN

1 5-Hydroxytryptamine (5-HT) receptors mediating contraction and relax ation are present in Cynomolgus monkey isolated jugular vein denuded o f endothelium. 2 In the absence of spasmogen, alpha-methyl-5-HT and su matriptan 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 mu M), followe d by relaxation (1 mu M - 32 mu M). The contractile effect of alpha-me thyl-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 spas mogen. 3 In tissues precontracted with U46619 (10 nM) and in the prese nce of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3, and 5-HT, receptor blockade, 5-C T and 5-MeOT caused endothelium-independent relaxation with potency va lues of 7.5 +/- 0.1 (n = 21) and 5.7 +/- 0.1 (n = 4), respectively. Th e potency of 5-HT was 7.2 (n = 2) while alpha-methyl-5-HT did not star t to relax the tissues below a concentration of 10 mu M. 4 Relaxations elicited by 5-CT were antagonized by the following compounds (with pK , values in parentheses): methiothepin (9.7), mesulergine (8.1), meter goline (8.0), clozapine (7.8), mianserin (7.7), spiperone (7.3), ritan serin (7.1), methysergide (7.0) and ketanserin (5.7). 5 It is conclude d that the 5-HT receptor mediating endothelium-independent relaxation may be a functional correlate of the putative 5-ht(7) receptor.