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Characterization of the 5‐HT receptor mediating endothelium‐dependent relaxation in porcine vena cava
Author(s) -
Sumner M.J.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12280.x
Subject(s) - ketanserin , methysergide , endothelium , endocrinology , medicine , 5 ht receptor , cyproheptadine , chemistry , endothelium derived relaxing factor , receptor , serotonin , biology
1 5‐Hydroxytryptamine (5‐HT) relaxes rings of neonatal porcine isolated vena cava by both an endothelium‐dependent and an endothelium‐independent mechanism. The receptor mediating the latter response has been shown to be a 5‐HT 1 ‐like receptor (positively coupled to adenylyl cyclase) located on the vascular smooth muscle. The features of the endothelium‐dependent response to 5‐HT in this preparation are now described. 2 In ring preparations contracted with the stable thromboxane‐A 2 ‐mimetic, U‐46619 (10 n m ), and in the presence of the 5‐HT 2 receptor antagonist ketanserin (1 μ m ), low concentrations of 5‐HT (1–100 n m ) evoked an endothelium‐dependent, rapid, ‘spike‐like’ relaxation. Higher concentrations of 5‐HT (0.1–10 μ m ) elicited a more sustained, but endothelium‐independent relaxation. 3 Relaxation induced by low concentrations (1–100 n m ) of 5‐HT was abolished by endothelium removal, and was markedly (but not totally) inhibited by the guanylate cyclase inhibitor, methylene blue (10 μ m ) or by the inhibitor of endothelium‐derived nitric oxide (NO) synthesis, l ‐N G ‐monomethylarginine ( l ‐NMMA; 100–500 μ m ). 4 The endothelium‐dependent response to 5‐HT was mimicked by α‐methyl‐5‐HT, 5‐methoxytryptamine, tryptamine and 2‐methyl‐5‐HT, but not by sumatriptan or 8‐hydroxy‐di‐n‐propylaminotetralin (8‐OH‐DPAT) at concentrations up to 10 μ m . In contrast, relaxation evoked by 5‐carboxamidotryptamine (5‐CT) was endothelium‐independent. 5 The endothelium‐dependent relaxation induced by 5‐HT or α‐methyl‐5‐HT was antagonized by methysergide, methiothepin, cyproheptadine and metergoline, but not by ketanserin, spiperone, ondansetron, verapamil, cyanopindolol, mesulergine, ICS 205–930, or indomethacin. 6 These results suggest that the endothelium‐dependent relaxation of porcine vena cava induced by 5‐HT is largely mediated by the release of NO (although other endothelium‐derived relaxing factors may also be involved) and that 5‐HT is acting at a receptor which is not ‘5‐HT 1 ‐like’, 5‐HT 2 , 5‐HT 3 or 5‐HT 4 and is not comparable to recognised 5‐HT receptor ligand binding sites. The characteristics of this receptor are discussed in relation to the endothelial 5‐HT receptor types in other blood vessels.