Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT2B receptors
Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT2B receptors
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DOI：
10.1038/sj.bjp.0703341
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发表时间：
2000-06-01
影响因子：
7.3
通讯作者：
Pertz, HH
中科院分区：
文献类型：
--
作者：
Glusa, E;Pertz, HH
1 使用选择性 5-HT2B 受体激动剂 BW 723C86 和多种结构多样的 5-HT 受体拮抗剂对介导猪肺动脉舒张的内皮 5-HT 受体进行了表征。2 如果用前列腺素 F-2 α (3 μM) 使具有完整内皮的动脉环预收缩。相对于 5-HT，BW 723C86 引起浓度依赖性松弛，pEC(50) = 8.21 +/- 0.03，E-max = 89 +/- 4%。 BW 723C86 的松弛反应可被 5-HT2B 受体拮抗剂 SB 204741、5-HT2B/2C 受体拮抗剂 SB 206553 和抗偏头痛药物苯噻替芬抑制，产生的 pA(2) 值分别为 6.68、7.20 和 8.32。针对 BW 723C86 的 pA(2) 值与针对 5-HT 测定的 pA(2) 值相似。3 5-HT 的松弛作用被 22 种不同化学结构的化合物拮抗。根据计算的平均 pA(2) 值，最有效拮抗剂的顺序为利坦色林 (9.38) > 美西麦角 (8.86) > 苯噻芬 (8.47) 大于或等于甲硫替平 (8.32) > LY 53857 (7.84) 大于或等于阿莫沙平 (7.80) 大于或等于洛沙平 (7.73) 大于或等于麦角林(7.64)大于或等于米安舍林(7.51)大于或等于萝沃尔辛(7.39)。具有弱阻断效力的化合物是育亨宾(6.37)、螺哌酮(5.88)和酮色林(5.85)。猪肺动脉拮抗剂的亲和力与人类和大鼠 5-HT2B 受体放射性配体结合研究的亲和力之间的相关性分析显示出高度显着的相关性（r = 0.95 和 0.84，P < 0.002 和 < 0.005）。与 5-HT2C 受体的相关性要低得多（r = 0.57，P = 0.035），与 5-ht(6) 和 5-HT7 受体没有相关性。 4 由此得出结论，介导猪肺动脉内皮依赖性舒张的 5-HT 受体属于 5-HT2B 亚型。
1 The endothelial 5-HT receptor mediating relaxation of pig pulmonary artery has been characterized using the selective 5-HT2B receptor agonist BW 723C86 and a variety of structurally diverse 5-HT receptor antagonists.2 If arterial rings with intact endothelium were precontracted with prostaglandin F-2 alpha (3 mu M). BW 723C86 caused concentration-dependent relaxation with a pEC(50) = 8.21 +/- 0.03 and E-max = 89 +/- 4% relative to 5-HT. The relaxant responses to BW 723C86 were inhibited by the 5-HT2B receptor antagonist SB 204741, the 5-HT2B/2C receptor antagonist SB 206553 and the antimigraine drug pizotifen, yielding pA(2) values of 6.68, 7.20 and 8.32, respectively. The pA(2) values against BW 723C86 were similar to those determined against 5-HT.3 The relaxant effect of 5-HT was antagonized by a variety of 22 compounds of diverse chemical structures. Based on the calculated mean pA(2) values the order of the most potent antagonists was ritanserin (9.38) > methysergide (8.86) > pizotifen (8.47) greater than or equal to methiothepin (8.32) > LY 53857 (7.84) greater than or equal to amoxapine (7.80) greater than or equal to loxapine (7.73) greater than or equal to metergoline (7.64) greater than or equal to mianserin (7.51) greater than or equal to rauwolscine (7.39). Compounds with weak blocking potency were yohimbine (6.37), spiperone (5.88) and ketanserin (5.85). Correlation analysis between the affinities of the antagonists in pig pulmonary artery and those from radioligand binding studies at human and rat 5-HT2B, receptors showed a highly significant correlation (r = 0.95 and 0.84, P < 0.002 and < 0.005). Correlation with 5-HT2C receptors was much lower (r = 0.57, P = 0.035), and no correlations were obtained with 5-ht(6) and 5-HT7 receptors.4 It is concluded that the 5-HT receptor mediating endothelium-dependent relaxation of pig pulmonary artery is of the 5-HT2B subtype.