左旋千金藤啶碱对大鼠纹体多巴氨受体亚型的作用特点

Study of the characteristic pharmacological property of stepholidine on dopamine subtype receptors of the striatum in rats

目的：研究左旋千金藤啶碱（SPD）和其同类物CSL、THPB10对大鼠纹状体D1、D2多巴胺（DA）受体作用特性。方法：24mA直流电刺激体外灌流之大鼠纹状体脑薄片，每5min收集灌流液测定[3H]DA释放量；分离大鼠纹状体突触体，用放免方法测定腺苷酸环化酶活性。结果：D2受体激动剂LY171555显著抑制电刺激诱发的[3H]DA释放，SPD、CSL和THPB10翻转LY171555的抑制作用，SPD、CSL、THPB10也诱发DA释放。在用Butaclamol封闭D2受体后，SPD和CSL以剂量依赖方式激活常敏大鼠纹状体突触体腺苷酸环化酶，而THPB10无作用。结论：合双羟基的SPD及其同类物CSL对DA受体不同亚型有激动／阻滞不同效应。

Objective: To investigate the pharmacological property of stepholidine (SPD) and its analogues as CSL and THPB10 on subtype receptors of the striatum in rats. Methods: Slices of the striatum ofthe rats, preincubated with 3H-dopamine (3H-Da), were superfused and stimulated with electricity. The efflux was collected in 5 min interval and the radiation of 3H-Da in the samples was measured to identify the Dareleased from the striatum slices. The synaptosomes of the striatum were prepared and the adenlage cyclaseactivity was determined with radioimmunoassay. Results: Ly171555, a selective D2 dopamine receptor agonist, significantly inhibited 3H-Da release evoked electrically from the striatal slices. This effect of Ly171555was antagonized or reversed by SPD, CSL and THPB10. The antagoning effect of CSL against Ly171555 indecreasing 3H-Da reIease was short-lived as compared wtih that of SPD and THPB10. lnterestingly to note,SPD, CSL and THPB10 themselves were obviously able to evoke 3H-Da release in the striatal slices withoutelectricity stimuIation. In the samples of striatal synatosomes, in which the D2Da receptors were blockedwith butaclamol, the activity of adenylate cycIase was significantly stimulated by SPD and CSL but not byTHPB10. Conclusion: These findings suggest that SPD and its analogue CSL possess 2 hydroxyl groups andexercise dual actions on D,.and D2 dopamine subtype receptors, agonist for D1 receptors and antagonist for D2receptors. THPB10, however, exercises antagonist action for D2 receptors only.