Nakamura S, Yue J L, Goshima Y, Miyamae T, Ueda H, Misu Y
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Neurosci Lett. 1994 Mar 28;170(1):22-6. doi: 10.1016/0304-3940(94)90229-1.
We attempted to clarify whether or not under inhibition of central dopa decarboxylase non-effective i.p. doses of L-dopa potentiate D2 receptor-mediated locomotor activities without conversion to dopamine in normal and i.v.t. 6-hydroxydopamine-treated rats. In normal rats, only the highest dose of quinpirole, a selective D2 agonist, at ranges used (0.01-1 mg/kg, s.c.) slightly increased the total counts of locomotor activities for 140 min after injection. A simultaneously injected non-effective dose of L-DOPA (30 mg/kg) potentiated locomotor activities by quinpirole (0.1 and 1 mg/kg). L-dopa potentiated quinpirole (1 mg/kg)-induced locomotor activities 90 to 140 min after the injection with marked increase in basal release of L-DOPA without increase in dopamine release simultaneously monitored during striatal microdialysis, compared to quinpirole alone. D-dopa (30 mg/kg) produced no potentiation. In 6-hydroxydopamine-treated rats, a non-effective dose of L-dopa (10 mg/kg) also potentiated quinpirole (0.3 mg/kg)-induced locomotor activities. L-dopa acting on a recognition site for itself stereoselectively potentiates postsynaptic D2 receptor-mediated locomotor activities of rats.
我们试图阐明，在中枢多巴脱羧酶受到抑制的情况下，无效的腹腔注射剂量的左旋多巴是否能在正常大鼠和经静脉注射6-羟基多巴胺处理的大鼠中，在不转化为多巴胺的情况下增强D2受体介导的运动活性。在正常大鼠中，在所使用的剂量范围内（0.01-1毫克/千克，皮下注射），只有最高剂量的喹吡罗（一种选择性D2激动剂）在注射后140分钟内略微增加了运动活性的总计数。同时注射的无效剂量的左旋多巴（30毫克/千克）增强了喹吡罗（0.1和1毫克/千克）诱导的运动活性。与单独使用喹吡罗相比，注射左旋多巴90至140分钟后，它增强了喹吡罗（1毫克/千克）诱导的运动活性，同时纹状体微透析期间监测到的左旋多巴基础释放显著增加，而多巴胺释放没有增加。D-多巴（30毫克/千克）没有产生增强作用。在经6-羟基多巴胺处理的大鼠中，无效剂量的左旋多巴（10毫克/千克）也增强了喹吡罗（0.3毫克/千克）诱导的运动活性。左旋多巴作用于其自身的识别位点，立体选择性地增强大鼠突触后D2受体介导的运动活性。
