Abstract

Serotonin (5-HT) at low concentrations induces an endothelium-dependent relaxation in the rat jugular vein mediated via a 5-HT1-like receptor. The receptor mediating this relaxation was characterized in vitro using agonists and antagonists in segments precontracted with prostaglandin F2 alpha in the presence of the 5-HT2 receptor antagonist ketanserin. The following substances acted as agonists, with the order of potency: 5-HT > dl-alpha-methyl-5-hydroxytryptamine = 5-carboxamidotryptamine > quipazine > 8-hydroxy-2-(dl-n-propylamino) tetralin. dl-Propranolol, mesulergine and mianserin acted as competitive, methysergide, 6-methyl-1-(1-methylethyl)-ergoline-8 beta-carboxylic acid 2-hydroxy-1-methylpropyl ester and sumatriptan as non-competitive, and ritanserin acted as both a competitive and non-competitive antagonist of the 5-HT-induced relaxation. Neither the 5-HT2 antagonists ketanserin and spiperone nor the 5-HT3 antagonist 1 alpha-H,3 alpha,5 alpha-H-tropan-3-yl,3,5-dichlorbenzoate affected the 5-HT-induced relaxation. The pEC50 values of the agonists and the pA2 and pAh values of the antagonists correlated strongly with pKD values at the 5-HT1C binding site. These results are consistent with a peripheral vascular 5-HT1C receptor in the rat jugular vein.