芳烷酮哌嗪类化合物SCP-1和SCP-2与5-HT_(1,2)受体的结合实验

Binding assay of 5-HT, and 5-HT_2 receptors by SCP-1 and SCP-2

目的:研究芳烷酮哌嗪类化合物SCP-1和SCP-2与5-HT1和5-HT2受体体外是否有结合作用。方法:5-HT1受体取材于大鼠大脑皮质,5-HT2受体取材于大鼠海马。采用受体-配体结合测定法测定10-3mol·L-1的SCP-1和SCP-2对5-HT1,5-HT2受体的最大结合率、半数抑制浓度(IC50)和Hill系数。结果:10-3mol·L-1的SCP-1和SCP-2与5-HT1受体的最大结合率分别为75％和63％。SCP-1和SCP-2与5-HT1受体结合的IC50分别为1．584和5．495μmol·L-1,二者与5-HT1受体结合的Hill系数分别为0．98和1．02。10-3mol·L-1的SCP-1和SCP-2与5-HT2受体的最大结合率分别为92％和87％。SCP-1和SCP-2与5-HT2受体结合的IC50分别为1．0和2．512μmol·L-1,二者与5-HT2受体结合的Hill系数分别为0．86和0．88。结论:SCP-1和SCP-2与5-HT1受体的结合方式是与单一受体位点结合,并且这种结合服从质量作用定律(Hill系数接近于1)。SCP-1和SCP-2与5-HT2受体呈现不规则性结合,也可能有负相互作用或多种结合位点(Hill系数偏离1)。

Objective： To investigate the binding of SCP-1 and SCP-2, aralkyl-ketone piperazine derivatives, to 5-HT1 and 5-HT2 receptors in vitro. Methods： 5-HT1 receptors were originated from cerebral cortex, and 5-HT2 receptors from hippocampus of rats. The binding assay of 5-HT1 and 5-HT2 receptors by SCP-1 and SCP-2 at the concentration of 10-3 mol. L^-1 was conducted by a radiolabeled ligand-receptor binding assay. Result： The maximal combination ratio of 5-HT1 receptors to SCP-1 and SCP-2 at 10-3 mol·L^-1 was 75% and 63% , respectively. The IC50 of SCP-1 and SCP-2 was 1. 584 and 5. 495 μmol· L^- 1. The Hill coefficient （nil） was 0.98 and 1.02, respectively. The maximal combination ratio of 5-HT2 receptors to SCP-1 and SCP-2 at 10-3 mol. L^-1 was 92% and 87%, respectively. The IC50 of SCP-1 and SCP-2 was 1.0 and 2. 512μmol＇L^-1,respectively. The Hill coefficient was 0. 86 and 0.88, respectively. Conclusion： SCP-1 and SCP-2 binds to 5-HT1 receptors at a single binding site （Hill coefficient of near 1 ）. The binding with 5-HT2 receptors is irregular or has negative interactions and several binding sites （Hill coefficient strayed from 1 ）.