Endothelium-dependent relaxation of porcine pulmonary arteries via 5-HT1C-like receptors

摘要: In PGF2α-precontracted pulmonary arteries with intact endothelium, 5-hydroxytryptamine (5-HT, 1.0-100 nmol/l) caused a concentration-dependent reversible relaxation, at higher concentrations the contractile response prevailed. endothelium-denuded vessels relaxation was absent. 5-HT-induced of precontracted probably mediated by release an endothelium-derived relaxing factor (EDRF). Preincubation methylene blue or NG-nitro-Lrarginine (200 μmol/l) attenuated relaxant effect. The accompanied increase in cGMP. Indomethacin (3 did not influence indicating that eicosanoids are involved to 5-HT. 5-HT1C and 5-HT2 receptor agonist α-methyl-5HT as potent 5-HT inducing relaxation. rank order potency agonists investigated α-methyl-5-HT > 5-methoxytryptamine tryptamine ω-methyl-5-HT 5-carboxamidotryptamine >2-methyl-5-HT 5,6-dihydroxytryptamine m-chlorophenylpiperazine >sumatriptan 8-OH-DPAT. Phentolamine, pindolol ICS 205-930 interfere antagonist ketanserin (1 inhibited but alter vasodilatation. Apart from blockade effects, mesulergine, cyproheptadine mianserin (0.1-3.0 μmol/l, each) induced parallel shift right concentration-response curve for a-methyl-5-HT Spiperone (0.3 exerted weak inhibitory effects on contraction. most (noncompetitive) against responses metitepine (0.1-1.0 which markedly depressed maximum effect agonists. failure inhibit suggests classical 5-HT3 receptors endothelium-dependent Comparison potencies antagonists their affinities brain binding sites revealed endothelial similar subtype. Furthermore, exhibit marked similarity recently cloned mediating contraction rat stomach fundus.