Svensson K, Carlsson A, Huff R M, Kling-Petersen T, Waters N
Department of Pharmacology, University of Göteborg, Sweden.
Eur J Pharmacol. 1994 Oct 3;263(3):235-43. doi: 10.1016/0014-2999(94)90718-8.
In an in vitro model for mitogenic activity in cloned Chinese hamster ovary (CHO) cells expressing rat dopamine D2 or D3 receptors, the EC50D2/EC50D3 ratios for the agonists, apomorphine, (+)-3-hydroxy-N-n-propyl-phenylpiperidine ((+)-3-PPP), quinpirole, R-(+)-7-hydroxy-2-(di-n-propylamino)tetralin (R-(+)-7-OH-DPAT) and pramipexole (SND919) were found to be 0.36, 0.41, 1.3, 3.7 and 7.0, respectively. In locomotor activity experiments with actively exploring rats, the more dopamine D3 preferring agonists, R-(+)-7-OH-DPAT and pramipexole, were most efficacious to reduce locomotion. The hypoactivity was also observed at doses that did not affect brain dopamine synthesis rate (DOPA accumulation) or release (measured in in vivo dialysis experiments). In contrast, for apomorphine, (+)-3-PPP and quinpirole there was a closer correlation between doses that reduced exploratory activity and doses that reduced brain dopamine release and synthesis. The present data support the hypothesis that the functional dopamine D3 receptor is a postsynaptic receptor inhibitory on rat locomotion.
在一个针对表达大鼠多巴胺D2或D3受体的克隆中国仓鼠卵巢（CHO）细胞促有丝分裂活性的体外模型中，发现激动剂阿扑吗啡、（+）-3-羟基-N-正丙基苯哌啶（（+）-3-PPP）、喹吡罗、R-（+）-7-羟基-2-（二正丙基氨基）四氢萘（R-（+）-7-OH-DPAT）和普拉克索（SND919）的EC50D2/EC50D3比值分别为0.36、0.41、1.3、3.7和7.0。在对积极探索的大鼠进行的运动活性实验中，更倾向于多巴胺D3的激动剂R-（+）-7-OH-DPAT和普拉克索在降低运动方面最有效。在不影响脑多巴胺合成速率（多巴积累）或释放（在体内透析实验中测量）的剂量下也观察到了活动减少。相比之下，对于阿扑吗啡、（+）-3-PPP和喹吡罗，降低探索活性的剂量与降低脑多巴胺释放和合成的剂量之间存在更密切的相关性。目前的数据支持这样一种假设，即功能性多巴胺D3受体是对大鼠运动具有抑制作用的突触后受体。
