Zier G, Drobny H, Valenta B, Singer E A
Institute of Pharmacology, University of Vienna, Austria.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):118-21. doi: 10.1007/BF00169488.
Slices prepared from rat cerebral cortex were labelled with 3H-noradrenaline and superfused. Electrical field stimulation was carried out 15 min (S1) and 45 min (S2) after the start of collection of 5-min samples using 4 pulses delivered at 100 Hz. Drugs acting at alpha 2-adrenoceptors were added 20 min before S2, and their effects were evaluated using the S2/S1-ratio. The alpha 2-adrenoceptor antagonists idazoxan (1 mumol/l) and rauwolscine (1 mumol/l) failed to increase stimulation-evoked overflow of radioactivity in the absence or presence of the noradrenaline reuptake inhibitor desipramine (1 mumol/l). This indicates that the duration of electrical stimulation was too short to allow development of alpha 2-adrenoceptor-mediated autoinhibition by released noradrenaline. The effect of clonidine (3-1000 nmol/l) on stimulation-evoked overflow of radioactivity was tested in the absence and presence of three different reuptake inhibitors (desipramine, 1 mumol/l; maprotiline, 1 mumol/l; cocaine, 10 mumol/l). The analysis yielded identical concentration-response curves under all conditions. These results argue against an action of inhibitors of neuronal reuptake of noradrenaline at the presynaptic alpha 2-adrenoceptor and against the concept of a functional link between uptake site and receptor.
将大鼠大脑皮层制备的切片用³H - 去甲肾上腺素标记并进行灌流。在开始收集5分钟样本后的15分钟（S1）和45分钟（S2）进行电场刺激，使用100赫兹的4个脉冲。在S2前20分钟加入作用于α₂ - 肾上腺素能受体的药物，并使用S2/S1比值评估其效果。在不存在或存在去甲肾上腺素再摄取抑制剂地昔帕明（1微摩尔/升）的情况下，α₂ - 肾上腺素能受体拮抗剂咪唑克生（1微摩尔/升）和萝芙辛（1微摩尔/升）未能增加刺激诱发的放射性溢出。这表明电刺激的持续时间太短，无法使释放的去甲肾上腺素产生α₂ - 肾上腺素能受体介导的自身抑制作用。在不存在和存在三种不同再摄取抑制剂（地昔帕明，1微摩尔/升；马普替林，1微摩尔/升；可卡因，10微摩尔/升）的情况下，测试可乐定（3 - 1000纳摩尔/升）对刺激诱发的放射性溢出的影响。分析在所有条件下得出相同的浓度 - 反应曲线。这些结果反对去甲肾上腺素神经元再摄取抑制剂在突触前α₂ - 肾上腺素能受体上的作用，也反对摄取位点与受体之间存在功能联系的概念。
