Hu G, Hu Y, Jin G Z
Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Zhongguo Yao Li Xue Bao. 1992 Jul;13(4):307-11.
Our results showed that l-stepholidine (l-SPD) inhibited basal Ca(2+)-ATPase activity in rat striatal synaptosomes with an IC50 of 31.5 mumol.L-1, suggesting its interaction with Ca2+ transport. l-SPD inhibited also calmodulin (CaM)-activated basal Ca(2+)-ATPase in a concentration-dependent manner. A complete reversal of CaM activation of Ca(2+)-ATPase was observed with l-SPD 10 mumol.L-1. The activity of synaptosomal Ca(2+)-ATPase and membrane-bound CaM level were decreased in haloperidol (1 mg.kg-1.d-1, ip) and l-SPD (5, 10, and 30 mg.kg-1.d-1, ip) treated rats for 7 and 14 d, respectively. But the activity of Ca(2+)-ATPase and membrane CaM level were increased after treatment with the same of doses haloperidol and l-SPD for 21 d. During the treatments with haloperidol and l-SPD cytosolic and nuclear CaM levels were not altered. These results suggest that l-SPD may modulate the release and synthesis of dopamine (DA) and the negative feedback regulation of presynaptic DA receptors by altering Ca2+ and CaM regulating processes in the central dopaminergic nervous system.
我们的结果表明，左旋千金藤啶碱（l-SPD）抑制大鼠纹状体突触体中的基础Ca(2+)-ATP酶活性，IC50为31.5 μmol·L-1，提示其与Ca2+转运相互作用。l-SPD还以浓度依赖性方式抑制钙调蛋白（CaM）激活的基础Ca(2+)-ATP酶。10 μmol·L-1的l-SPD可使CaM对Ca(2+)-ATP酶的激活作用完全逆转。分别用氟哌啶醇（1 mg·kg-1·d-1，腹腔注射）和l-SPD（5、10和30 mg·kg-1·d-1，腹腔注射）处理大鼠7天和14天，突触体Ca(2+)-ATP酶活性和膜结合CaM水平降低。但用相同剂量的氟哌啶醇和l-SPD处理21天后，Ca(2+)-ATP酶活性和膜CaM水平升高。在氟哌啶醇和l-SPD处理期间，胞质和核CaM水平未改变。这些结果表明，l-SPD可能通过改变中枢多巴胺能神经系统中Ca2+和CaM调节过程来调节多巴胺（DA）的释放和合成以及突触前DA受体的负反馈调节。
