Zhang X X, Zhu Z T, Jin G Z
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, PR China.
Life Sci. 1998;63(7):537-44. doi: 10.1016/s0024-3205(98)00304-x.
(-)-Stepholidine(SPD), isolated from the Chinese herb Stephania, is demonstrated to be a DA antagonist, but it also shows D1 agonistic action on rotational behavior in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. The present study further ascertains its D1 agonistic property on firing activity of globus pallidus (GP) in control and 6-OHDA-lesioned rats. In the control rats, the firing activities of the GP neurons elicited by DA agonists (i.v.), such as apomorphine (D1/D2), SKF38393 (D1), and LY171555 (D2), were readily reversed by SPD (4 mg/kg, i.v.); but SPD, per se, induced variable alterations. In the 6-OHDA-lesioned rats, apomorphine, SKF38393 and LY171555 displayed the marked inhibition as well as excitation on the unit firing. The individual firing variations (87.1+/-17.8, 55.1+/-15.7 and 62.1+/-16.7%, respectively) were much larger than those in the control group, and were completely abolished by SPD (2 mg/kg). However, SPD also showed D1 partial agonistic action on the GP neuron firing. Moreover, the pre-blockade of D2 receptors with spiperone (0.5 mg/kg, i.v.), SPD exhibited the D1 agonist action which was reversed by the D1 antagonist SCH23390. These results suggest that SPD has a dual action on the GP neuron firing in the 6-OHDA-lesioned rats, i.e., antagonist to D2 DA receptors and partial agonist to D1 receptors.
从中药千金藤中分离得到的（-）-千金藤啶碱（SPD）被证明是一种多巴胺（DA）拮抗剂，但它对单侧6-羟基多巴胺（6-OHDA）损伤大鼠的旋转行为也表现出D1激动作用。本研究进一步确定了其对正常和6-OHDA损伤大鼠苍白球（GP）放电活动的D1激动特性。在正常大鼠中，DA激动剂（静脉注射）如阿扑吗啡（D1/D2）、SKF38393（D1）和LY171555（D2）引发的GP神经元放电活动很容易被SPD（4mg/kg，静脉注射）逆转；但SPD本身会引起不同的变化。在6-OHDA损伤大鼠中，阿扑吗啡、SKF38393和LY171555对单位放电表现出明显的抑制以及兴奋作用。个体放电变化（分别为87.1±17.8、55.1±15.7和62.1±16.7%）比对照组大得多，并被SPD（2mg/kg）完全消除。然而，SPD对GP神经元放电也表现出D1部分激动作用。此外，用螺哌隆（0.5mg/kg，静脉注射）预先阻断D2受体后，SPD表现出D1激动作用，该作用可被D1拮抗剂SCH23390逆转。这些结果表明，SPD对6-OHDA损伤大鼠的GP神经元放电有双重作用，即对D2 DA受体为拮抗剂，对D1受体为部分激动剂。
