左旋千金藤啶碱对外周血管多巴胺DA_1和DA_2受体亚型的作用

EFFECTS OF l STEPHOLIDINE ON THE PERIPHERAL VASCULAR DOPAMINE DA 1 AND DA 2 RECEPTOR SUBTYPES

用家兔离体血管环方法，研究左旋千金藤啶碱（ｌＳＰＤ）对外周血管ＤＡ１和ＤＡ２受体亚型的作用。结果表明，ｌＳＰＤ使ＤＡ１受体激动剂ＦＯＤＡ诱发的肾、肺和肠动脉以及ＤＡ２受体激动剂ＰＢＤＡ诱发的肠和股动脉舒张反应的量效曲线非平行右移，最大反应（Ｅｍａｘ）降低，均呈非竞争性拮抗；ｌＳＰＤ本身还可使肾和肺血管产生轻度的浓度依赖性舒张反应，表现为ＤＡ１受体激动剂的作用特性。提示ｌＳＰＤ为外周血管ＤＡ１和ＤＡ２受体的混合性阻滞剂并兼有ＤＡ１受体部分激动剂的双重作用特性。

The effects of l stepholidine( l SPD) on peripheral vascular dopamine DA 1 and DA 2 receptors were studied using isolated vascular rings in rabbits. It was shown that (1) l SPD(0 1～10 μmol·L -1 ) shifted the dose response curves to the right in a nonparallel fashion and decreased the maximal response (Emax) of both the fenoldopam(FODA, a selective DA 1 agonist) induced and the propyl buty dopamine(PBDA, a selective DA 2 agonist) induced vasorelaxation showing a non competitive antagonistic action. The pD 2 values of l SPD for FODA in the renal, pulmonary and mesenteric arteries were 5 43, 5 48 and 5 58, respectively. The pD 2 values for PBDA in the mesenteric and femoral arteries were 5 35 and 5 89, respectively. The potencies of its antagonistic action were comparable to SCH23390, a selective DA 1 antagonist, and to domperidone, a selective DA 2 antagonist. (2) l SPD(0 1～100 μmol·L -1 ) per se was also found to induce slight but dose related vasorelaxations in the renal and pulmonary arteries displaying its DA 1 agonistic activity. Its pD 2 values were 4 98 and 5 02, respectively. However, its Emax were considerably smaller than that of FODA. These results suggest that l SPD is a mixed peripheral DA 1 and DA 2 receptor antagonists and weak DA 1 receptor agonist with pharmacological property of dual action.