Jones S R, Garris P A, Kilts C D, Wightman R M
Curriculum in Neurobiology, University of North Carolina at Chapel Hill, USA.
J Neurochem. 1995 Jun;64(6):2581-9. doi: 10.1046/j.1471-4159.1995.64062581.x.
Regional differences in the kinetics and pharmacological inhibition of dopamine uptake were investigated with fast-scan cyclic voltammetry in both the intact rat brain and a brain slice preparation. The regions compared were the basolateral amygdaloid nucleus, caudate-putamen, and nucleus accumbens. The frequency dependence of dopamine efflux evoked in vivo by electrical stimulation of the medial forebrain bundle was evaluated by nonlinear curve fitting with a Michaelis-Menten-based kinetic model. The Km for dopamine uptake was found to be significantly higher in the basolateral amygdala (0.6 microM) than in the other two regions (0.2 microM), whereas the Vmax value for dopamine uptake in the basolateral amygdala was significantly lower (0.49 microM/s vs. 3.8 and 2.4 microM/s in the caudate and accumbens, respectively). Similar kinetics were also obtained in brain slices. Addition of a dopamine uptake inhibitor, cocaine or nomifensine (10 microM), to the perfusion buffer increased the apparent Km value > 25-fold in slices of both the caudate-putamen and nucleus accumbens. In contrast, neither uptake inhibitor had an observable effect in the basolateral amygdaloid nucleus. Thus, dopamine uptake in the rat brain is regionally distinct with regard to rate, affinity, and sensitivity to competitive inhibition.
利用快速扫描循环伏安法，在完整大鼠脑和脑片标本中研究了多巴胺摄取动力学和药理学抑制的区域差异。所比较的区域为基底外侧杏仁核、尾状核 - 壳核和伏隔核。通过基于米氏动力学模型的非线性曲线拟合，评估了内侧前脑束电刺激在体内诱发的多巴胺流出的频率依赖性。发现基底外侧杏仁核中多巴胺摄取的米氏常数（Km）（0.6微摩尔）显著高于其他两个区域（0.2微摩尔），而基底外侧杏仁核中多巴胺摄取的最大反应速度（Vmax）值则显著较低（分别为0.49微摩尔/秒，而尾状核和伏隔核中分别为3.8和2.4微摩尔/秒）。在脑片中也获得了类似的动力学结果。向灌注缓冲液中添加多巴胺摄取抑制剂可卡因或诺米芬辛（10微摩尔），使尾状核 - 壳核和伏隔核切片中的表观Km值增加超过25倍。相比之下，两种摄取抑制剂在基底外侧杏仁核中均未产生明显作用。因此，大鼠脑中多巴胺摄取在速率、亲和力和对竞争性抑制的敏感性方面存在区域差异。
