MEDIATION BY 5-HYDROXYTRYPTAMINE(2B) RECEPTORS OF ENDOTHELIUM-DEPENDENT RELAXATION IN RAT JUGULAR-VEIN

1 An 'atypical' 5-HT2 receptor which is located on the endothelium of rat jugular vein has been described. In the present study we have further defined the nature of the 5-HT2 receptor subtype present in this preparation. 2 In experiments conducted in the presence of ketanserin to preclude involvement of 5-HT2 receptors, the mixed 5-HT2B/(2C) antagonist, SB 200646, acted as an antagonist of 5-HT at the endothelial 5-HT receptor (pA(2) = 7.2). Yohimbine, which exhibits negligible affinity for rat 5-HT2C, receptors but has high 5-HT2B receptor affinity, acted as a potent but non-surmountable antagonist (pA(2) greater than or equal to 7.3) in rat jugular vein. Neither yohimbine nor SB 200646 affected endothelium-dependent relaxations induced by carbachol. 3 Mianserin also acted as a surmountable antagonist (pA(2) = 7.3) and the 5-HT2B agonist, BW 723C86, acted as a potent partial agonist (pEC(50) [95% C L], intrinsic activity +/- s.e.mean = 7.9 [7.6-8.3], 0.84 +/- 0.04). Responses to BW 723C86 were antagonized by SB 200646 (0.3 mu M) yielding an 'apparent' pA(2) [95% CL] of 7.03 [6.76-7.32]. 4 These data are consistent with the presence of 5-HT2B receptors mediating endothelium-dependent relaxation of rat jugular vein.