Inoue O, Wakahara S, Kobayashi K, Gee A
Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Japan.
J Neural Transm (Vienna). 1999;106(2):131-7. doi: 10.1007/s007020050145.
The effect of acute pretreatment with MK-801 on the binding in vivo of both 3H-N-methylspiperone (NMSP) and 3H-raclopride (RAC) were compared in mice. In the striatum, MK-801 significantly increase 3H-NMSP binding, whereas no significant alterations in 3H-RAC binding were seen. In contrast, binding in the cerebral cortex of both radiolabeled ligands was not changed by MK-801. Kinetic analysis revealed that the increase in 3H-NMSP binding induced by MK-801 was due to an increase in the rate constant k3(k3 = kon.Bmax). In vivo saturation experiments showed that Bmax for 3H-NMSP binding was relatively unchanged and an increase in the apparent association rate constant (kon) was the main reason for an increase in the k3 for 3H-NMSP binding. As 3H-RAC binding is known to be much more sensitive to competitive inhibition than is 3H-NMSP binding, these results strongly suggest that factors other than competition by endogenous dopamine may contribute to changes in receptor binding in vivo caused by NMDA-antagonism.
比较了MK - 801急性预处理对小鼠体内3H - N - 甲基螺哌隆（NMSP）和3H - 雷氯必利（RAC）结合的影响。在纹状体中，MK - 801显著增加3H - NMSP的结合，而3H - RAC的结合未见明显改变。相比之下，MK - 801对两种放射性标记配体在大脑皮层的结合没有影响。动力学分析表明，MK - 801诱导的3H - NMSP结合增加是由于速率常数k3（k3 = kon.Bmax）增加所致。体内饱和实验表明，3H - NMSP结合的Bmax相对不变，表观缔合速率常数（kon）增加是3H - NMSP结合k3增加的主要原因。由于已知3H - RAC结合比3H - NMSP结合对竞争性抑制更敏感，这些结果强烈表明，除内源性多巴胺竞争外的其他因素可能导致NMDA拮抗剂引起的体内受体结合变化。
