title: Differential classification of vascular smooth muscle and endothelial cell 5-HT receptors by use of tryptamine analogues.
abstract: In ring preparations of the rabbit external jugular vein contracted with the thromboxane-mimetic U-46619, submicromolar concentrations of 5-hydroxytryptamine (5-HT) and chemically related analogues produced relaxations that were dependent on the integrity of the vascular endothelium. The receptor mediating endothelium-dependent relaxations was evidently similar to previously described endothelial 5-HT receptors since relaxation responses to alpha-methyl-5-HT were not blocked by atropine, (+/-)-propranolol, yohimbine, indomethacin, ketanserin or MDL-72222, but were non-competitively antagonized by methysergide, methiothepin and cyproheptadine. The activities of some tryptamine agonists and antagonists at the endothelial 5-HT receptor in rabbit jugular vein were compared with their activities at the smooth muscle 5-HT2-receptor in rabbit aortic rings. Differences in the tryptamines' affinities and relative efficacies showed that the endothelial 5-HT receptor was not of the 5-HT2-type. The high agonist potencies of 5-HT and 5-carboxamidotryptamine, the susceptibility to antagonism by both methiothepin and methysergide and the resistance to blockade by selective 5-HT2 and 5-HT3 ('M') receptor antagonists implies that the endothelial receptor belongs to the '5-HT1-like' class. However, the agonist potency order 5-HT = alpha-methyl-5-HT greater than 5-carboxamidotryptamine suggested that the receptor is not the same as the peripheral '5-HT1-like' receptors reported to mediate directly contraction of the dog saphenous vein or relaxation of vascular and non-vascular smooth muscles. At these receptors, the potency order is 5-carboxamidotryptamine greater than 5-HT greater than alpha-methyl-5-HT. These results constitute preliminary evidence that peripheral '5-HT1-like' receptors, like central 5-HT1 recognition sites, are a heterogeneous population. Further comparative studies with a wider range of receptor probes are necessary to establish whether or not these receptors represent functional counterparts of the ligand binding sites in the brain.
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects*; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014363:Tryptamines; C042390:alpha-methylserotonin; D012701:Serotonin