Allard P O, Eriksson K, Ross S B, Marcusson J O
Department of Psychiatry, University of Umeå, Sweden.
Neuropsychobiology. 1990;23(4):177-81. doi: 10.1159/000119449.
The binding of the selective dopamine uptake inhibitor [3H]GBR-12935 to rat striatum was studied. Competition by mazindol and dopamine against [3H]GBR-12935 binding revealed monophasic binding curves. The addition of 100 microM dopamine to the mazindol competition inhibited only 80% of the binding, indicating more than one [3H]GBR-12935 binding site in rat striatum. When a binding fraction that could be discriminated by 1 microM mazindol or 1 mM dopamine was defined as specific binding, a single site binding model was obtained. The [3H]GBR-12935 binding was of protein nature, since it was abolished after protease treatment. Drug inhibition studies with the addition of low concentrations of mazindol and dopamine resulted in alterations in apparent Kd values only, suggesting competitive inhibition by these compounds against [3H]GBR-12935 binding. It is concluded that the [3H]GBR-12935 binding to rat striatum discriminated by 1 microM mazindol reflects binding to the substrate recognition site for the dopamine uptake.
研究了选择性多巴胺摄取抑制剂[3H]GBR - 12935与大鼠纹状体的结合情况。马吲哚和多巴胺对[3H]GBR - 12935结合的竞争显示出单相结合曲线。在马吲哚竞争实验中加入100微摩尔多巴胺仅抑制了80%的结合，这表明大鼠纹状体中存在不止一个[3H]GBR - 12935结合位点。当将可被1微摩尔马吲哚或1毫摩尔多巴胺区分的结合部分定义为特异性结合时，得到了一个单位点结合模型。[3H]GBR - 12935的结合具有蛋白质性质，因为蛋白酶处理后结合被消除。加入低浓度马吲哚和多巴胺的药物抑制研究仅导致表观解离常数（Kd）值发生改变，表明这些化合物对[3H]GBR - 12935结合具有竞争性抑制作用。结论是，被1微摩尔马吲哚区分的[3H]GBR - 12935与大鼠纹状体的结合反映了与多巴胺摄取底物识别位点的结合。
